[Federal Register: December 3, 2007 (Volume 72, Number 231)]
[Rules and Regulations]
[Page 67850-67852]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr03de07-6]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1300
[Docket No. DEA-260F]
RIN 1117-AA94
Definition of ``Positional Isomer'' as It Pertains to the Control
of Schedule I Controlled Substances
AGENCY: Drug Enforcement Administration (DEA), Department of Justice.
ACTION: Final Rule.
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SUMMARY: On May 25, 2006, DEA published a Notice of Proposed Rulemaking
which proposed the addition of a specific definition for the term
``positional isomer'' to allow for the systematic determination of
which isomers of schedule I substances would be considered to be
``positional,'' and therefore, subject to schedule I control. This
rulemaking finalizes that definition.
The Controlled Substances Act (CSA) and its implementing
regulations specify which hallucinogenic substances are considered
schedule I controlled substances. The CSA states that all salts,
isomers, and salts of isomers of these substances are also schedule I
controlled substances. In non-technical terms, an isomer of a substance
is a different compound, but a compound which has the same number and
kind of atoms. The terms ``optical isomer'' and ``geometric isomer''
are specific scientific terms and it is easy to determine whether one
substance is an optical or geometric isomer of another. The term
``positional isomer,'' however, is subject to scientific
interpretation.
The addition of a definition for the term ``positional isomer''
will assist legitimate research[ers] and industry in determining the
control status of materials that are ``positional isomers'' of schedule
I hallucinogens. While the DEA will remain the authority for ultimately
determining the control status of a given material, providing a
specific definition for ``positional isomer'' will ensure consistent
criteria are utilized in making these determinations.
This rule does not change existing laws, regulations, policies,
processes, and procedures regarding the determination of control status
for schedule I hallucinogenic substances. This rule merely makes
available to the public the longstanding definition of ``positional
isomer'' which DEA has used when making these scheduling
determinations.
This rule is relevant only to specialized forensic or research
chemists. Most of these individuals are existing DEA registrants who
are authorized by the DEA to handle schedule I hallucinogenic
substances.
DATES: Effective January 2, 2008.
FOR FURTHER INFORMATION CONTACT: Christine A. Sannerud, Ph.D., Chief,
Drug and Chemical Evaluation Section, Office of Diversion Control, Drug
Enforcement Administration, Washington, DC 20537 at (202) 307-7183.
SUPPLEMENTARY INFORMATION:
Background
On May 25, 2006, DEA published a Notice of Proposed Rulemaking
(NPRM) [71 FR 30097] which proposed the addition of a specific
definition for the term ``positional isomer.'' As DEA discussed in the
NPRM, in many instances, the control of a substance under the CSA often
includes the specific substance listed under the CSA, as well as the
substance's salts, isomers, and/or salts of isomers. In most instances,
the term isomer includes only optical isomers. In other instances,
however, the term isomer includes positional and/or geometric isomers.
As DEA discussed in its NPRM, in non-technical terms, isomers are
different compounds that have the same molecular formula (the same
number and types of atoms). The terms ``optical isomer'' and
``geometric isomer'' are specifically defined and well understood
scientific terms, and it is easy to determine whether one substance is
an optical or geometric isomer of another. The term ``positional
isomer,'' however, is not universally defined, and, therefore, is
subject to scientific interpretation. In order to ensure that
consistent criteria are utilized in determining whether one substance
is considered a ``positional isomer'' of another, the DEA is
establishing a specific definition for ``positional isomer.'' This
definition will be added to 21 CFR 1300.01(b)(21).
Existing CSA and CFR References to ``Positional Isomers''
The CSA and its implementing regulations (21 CFR 1308.11(d))
specify which hallucinogenic substances are considered schedule I
controlled substances. Under the CSA and its implementing regulations,
there are only three references to the term ``positional isomer'':
(1) Pursuant to 21 U.S.C. 802(14), ``the term `isomer' means the
optical isomer, except as used in schedule I(c) and schedule II(a)(4).
As used in schedule I(c), the term `isomer' means any optical,
positional, or geometric isomer. As used in schedule II(a)(4), the term
`isomer' means any optical or geometric isomer.''
(2) Under 21 CFR 1300.01(b)(21), ``The term `isomer' means the
optical isomer, except as used in Sec. Sec. 1308.11(d) and
1308.12(b)(4) of this chapter. As used in Sec. 1308.11(d) of this
chapter, the term `isomer' means the optical, positional, or geometric
isomer. As used in Sec. 1308.12(b)(4) of this chapter, the term
`isomer' means the optical or geometric isomer.''
(3) 21 CFR 1308.11(d) states, ``Hallucinogenic substances. Unless
specifically excepted or unless listed in another schedule, any
material, compound, mixture, or preparation, which contains any
quantity of the following hallucinogenic substances, or which contains
any of its salts, isomers, and salts of isomers whenever the existence
of such salts, isomers, and salts of isomers is possible within the
specific chemical designation (for purposes of this paragraph only, the
term 'isomer' includes the optical, positional and geometric
isomers).''
Why Definition Is Needed
As DEA discussed in the NPRM, the CSA (21 U.S.C. 802(14) and 21
U.S.C. 812(c)(I)(c)) and its implementing regulations (21 CFR
1308.11(d)) specify which hallucinogenic substances are considered
schedule I controlled substances. The CSA further states that all
salts, isomers, and salts of isomers of these substances are also
schedule I controlled substances.
Under the definition of ``isomer'' found in 21 CFR 1300.01(b)(21),
``The term `isomer' means the optical isomer, except as used in
Sec. Sec. 1308.11(d) and 1308.12(b)(4) of this chapter. As used in
Sec. 1308.11(d) of this chapter, the term `isomer' means the optical,
positional, or geometric isomer. As used in Sec. 1308.12(b)(4) of this
chapter, the term `isomer' means the optical or geometric isomer.''
Therefore, according to this definition as it specifically applies
to hallucinogens, the term ``isomer'' includes all optical, positional,
or geometric isomers. As such, all salts, isomers (including optical,
positional, or geometric isomers), and salts of isomers (including
optical, positional, or geometric isomers) of the hallucinogenic
substances listed in 21 U.S.C. 812(c)(I)(c) and 21 CFR 1308.11(d) are
considered schedule I controlled substances.
[[Page 67851]]
Because the determination as to whether a substance is considered a
``positional isomer'' can be subject to scientific interpretation, the
DEA believes it is necessary to specifically define the term
``positional isomer''. This definition will only pertain to those
substances that are ``positional isomers'' of schedule I controlled
substances pursuant to 21 U.S.C. 812(c)(I)(c) and 21 CFR 1308.11(d).
As DEA noted in the NPRM, DEA is not establishing definitions for
either optical or geometric isomers. The DEA believes that these terms
are highly specific and are not subject to differing scientific
interpretation.
Comments
The definition of ``positional isomer'' will be used in the
determination of the control status of substances as schedule I
controlled substances pursuant to 21 CFR 1308.11(d). This definition is
highly technical in nature and the DEA has sought to provide specific
criteria for determination as to whether a substance is a ``positional
isomer'' of schedule I hallucinogens. In writing the definition
contained in this rulemaking, DEA consulted a wide variety of reference
sources including, but not limited to, Chemical Abstracts, the IUPAC
Compendium of Chemical Terminology, World Health Organization (WHO)
documents, and various encyclopedias and chemistry textbooks.
The NPRM sought input from all interested parties regarding the
proposed definition of ``positional isomer.'' DEA received one comment
in response to the proposed definition. That comment did not raise any
specific objections to the definition, but expressed the opinion that
instead of DEA adding this definition, this duty should be the
responsibility of Congress and the definition added via legislation.
DEA disagrees. 21 U.S.C. 821 authorizes the Attorney General to
``promulgate rules and regulations and to charge reasonable fees
relating to the registration and control of the manufacture,
distribution, and dispensing of controlled substances.'' Expanding on
this authority, 21 U.S.C. 871(b) further provides that the Attorney
General ``may promulgate and enforce any rules, regulations, and
procedures which he may deem necessary and appropriate for the
efficient execution of his functions.'' The authority has been
delegated by the Attorney General to the Administrator of DEA pursuant
to 28 CFR 0.100, and redelegated to the Deputy Administrator pursuant
to 28 CFR 0.104.
It is, therefore, well within the Deputy Administrator's purview to
issue a notice of proposed rulemaking to define a term relating to the
control of certain schedule I controlled substances. By inviting
comment to the proposed definition, DEA ensured that potentially
affected persons, such as researchers, were given the opportunity to
review the definition and submit comments or changes. No other comments
were received by DEA. Therefore, this rulemaking finalizes the
definition exactly as it was proposed in the NPRM.
Criteria That Will Apply to Positional Isomers
Pursuant to 21 U.S.C. 802(14), 21 U.S.C. 812(c)(I)(c), and 21 CFR
1308.11(d), positional isomers of schedule I hallucinogens are any and
all substances which:
(1) Are not already controlled in a different schedule I category,
or are listed in another schedule, or are specifically exempted from
control by law; and
(2) Have the same molecular formula and core structure as a
schedule I hallucinogen; and
(3) Have the same functional group(s) and/or substituent(s) as
those found in the respective schedule I hallucinogen, attached at any
position(s) on the core structure, but in such manner that no new
chemical functionalities are created and no existing chemical
functionalities are destroyed relative to the respective schedule I
hallucinogen; except that
(4) Rearrangements of alkyl moieties within or between functional
group(s) or substituent(s), or divisions or combinations of alkyl
moieties, that do not create new chemical functionalities or destroy
existing chemical functionalities, would be within the definition of
positional isomer (and therefore be controlled).
As clarification, note that the ``core structure'' is the parent
molecule that is the common basis for the class; for example,
tryptamine, phenethylamine, or ergoline. The following are examples of
rearrangements resulting in creation and/or destruction of chemical
functionalities. These rearrangements result in compounds which are not
positional isomers: ethoxy to alpha-hydroxyethyl, hydroxy and methyl to
methoxy, or the repositioning of a phenolic or alcoholic hydroxy group
to create a hydroxyamine. Examples of rearrangements resulting in
compounds that would be positional isomers include, but are not limited
to: tert-butyl to sec-butyl, methoxy and ethyl to isopropoxy, N,N-
diethyl to N-methyl-N-propyl, or alpha-methylamino to N-methylamino.
Impact of Rule Limited to Specialized Forensic or Research Chemists
As DEA discussed in the NPRM, the addition of a definition for the
term ``positional isomer'' as it applies to 21 CFR 1308.11(d) will
assist legitimate research[ers] and industry in determining the control
status of substances that are isomers of schedule I hallucinogens.
While the DEA will remain the authority on ultimately determining the
control status of a given substance, providing a specific definition
for ``positional isomer'' will greatly reduce any potential confusion
or inconsistencies in making these determinations.
This definition will enable researchers and industry to determine
definitively whether a substance is a ``positional isomer'' of a
schedule I hallucinogen. As such, they will be able to know the control
status of a particular substance when considering new research.
This rule is relevant only to specialized forensic or research
chemists. Most of these individuals are existing DEA registrants who
are authorized by the DEA to handle schedule I hallucinogenic
substances.
Specific Changes and Definition
As currently defined in 21 CFR 1300.01(b)(21), the term ``isomer''
means the optical isomer, except as used in Sec. 1308.11(d) and Sec.
1308.12(b)(4) of this chapter. As used in Sec. 1308.11(d) of this
chapter, the term ``isomer'' means any optical, positional, or
geometric isomer. As used in Sec. 1308.12(b)(4) of this chapter, the
term ``isomer'' means any optical or geometric isomer.
Pursuant to this Final Rule, 21 CFR 1300.01(b)(21) is revised to
include a specific definition for the term ``positional isomer''. The
modification specifies that, as used in Sec. 1308.11(d), the term
``positional isomer'' means any substance possessing the same molecular
formula and core structure and having the same functional group(s) and/
or substituent(s) as those found in the respective schedule I
hallucinogen, attached at any position(s) on the core structure, but in
such manner that no new chemical functionalities are created and no
existing chemical functionalities are destroyed relative to the
respective schedule I hallucinogen. Rearrange ments of alkyl moieties
within or between functional group(s) or substituent(s), or divisions
or combinations of alkyl moieties that do not create new chemical
functionalities or destroy existing chemical functionalities, would be
within the
[[Page 67852]]
definition of positional isomer. For purposes of this definition, the
``core structure'' is the parent molecule that is the common basis for
the class. Some examples would include tryptamine, phenethylamine, or
ergoline. Examples of non-permissible rearrangements resulting in
creation and/or destruction of chemical functionalities (that therefore
would not be considered positional isomers) include, but are not
limited to: ethoxy to alpha-hydroxyethyl, hydroxy and methyl to
methoxy, or the repositioning of a phenolic or alcoholic hydroxy group
to create a hydroxyamine. Examples of permissible rearrangements (that
are within the definition of positional isomers) include: tert-butyl to
sec-butyl, methoxy and ethyl to isopropoxy, N,N-diethyl to N-methyl-N-
propyl, or alpha-methylamino to N-methylamino.
Scientific/Technical Nature of Definition
As DEA discussed in its NPRM, DEA understands that the definition
is highly technical and laden with scientific terms. However, the DEA
believes that such a highly technical definition is necessary to ensure
that consistent criteria are utilized in determining whether one
substance is a ``positional isomer'' of another.
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. 605(b)), has reviewed this regulation, and by approving it
certifies that this regulation will not have a significant economic
impact on a substantial number of small entities. The inclusion of the
definition of positional isomer set forth herein is unlikely to subject
any new substances to CSA control. Also, this rule does not require the
obtaining of new DEA registrations. Most persons affected by this rule
are already DEA registrants (or would have to become registrants even
absent this rule in order to handle schedule I hallucinogens). Further,
this rule does not impose any additional regulatory burden on the
regulated community. The change simply will ensure that consistent
criteria are utilized in making scheduling determinations.
Executive Order 12866
The Deputy Administrator further certifies that this rulemaking has
been drafted in accordance with the principles in Executive Order 12866
Sec. 1(b). It has been determined that this is a significant
regulatory action. Therefore, this action has been reviewed by the
Office of Management and Budget.
Executive Order 12988
This regulation meets the applicable standards set forth in
Sec. Sec. 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.
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 $114,000,000 or more; a major increase in
costs 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
Controlled substances, Definitions, Drug Traffic Control.
0
For the reasons set out above, 21 CFR part 1300 is amended as follows:
PART 1300--DEFINITIONS [AMENDED]
0
1. The authority citation for Part 1300 continues to read as follows:
Authority: 21 U.S.C. 802, 871(b), 951, 958(f).
0
2. Section 1300.01 is amended by revising paragraph (b)(21) to read as
follows:
Sec. 1300.01 Definitions relating to controlled substances.
* * * * *
(b) * * *
(21) (i) The term isomer means the optical isomer, except as used
in Sec. 1308.11(d) and Sec. 1308.12(b)(4) of this chapter. As used in
Sec. 1308.11(d) of this chapter, the term ``isomer'' means any
optical, positional, or geometric isomer. As used in Sec.
1308.12(b)(4) of this chapter, the term ``isomer'' means any optical or
geometric isomer.
(ii) As used in Sec. 1308.11(d) of this chapter, the term
``positional isomer'' means any substance possessing the same molecular
formula and core structure and having the same functional group(s) and/
or substituent(s) as those found in the respective schedule I
hallucinogen, attached at any position(s) on the core structure, but in
such manner that no new chemical functionalities are created and no
existing chemical functionalities are destroyed relative to the
respective schedule I hallucinogen. Rearrangements of alkyl moieties
within or between functional group(s) or substituent(s), or divisions
or combinations of alkyl moieties, that do not create new chemical
functionalities or destroy existing chemical functionalities, are
allowed i.e., result in compounds which are positional isomers. For
purposes of this definition, the ``core structure'' is the parent
molecule that is the common basis for the class; for example,
tryptamine, phenethylamine, or ergoline. Examples of rearrangements
resulting in creation and/or destruction of chemical functionalities
(and therefore resulting in compounds which are not positional isomers)
include, but are not limited to: ethoxy to alpha-hydroxyethyl, hydroxy
and methyl to methoxy, or the repositioning of a phenolic or alcoholic
hydroxy group to create a hydroxyamine. Examples of rearrangements
resulting in compounds which would be positional isomers include: tert-
butyl to sec-butyl, methoxy and ethyl to isopropoxy, N,N-diethyl to N-
methyl-N-propyl, or alpha-methylamino to N-methylamino.
* * * * *
Dated: November 21, 2007.
Michele M. Leonhart,
Deputy Administrator,
[FR Doc. E7-23413 Filed 11-30-07; 8:45 am]
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