[Federal Register Volume 71, Number 101 (Thursday, May 25, 2006)]
[Proposed Rules]
[Pages 30097-30100]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-7979]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1300

[Docket No. DEA-260P]
RIN 1117-AA94


Definition of ``Positional Isomer'' as It Pertains to the Control 
of Schedule I Controlled Substances

AGENCY: Drug Enforcement Administration (DEA), U.S. Department of 
Justice.

ACTION: Notice of proposed rulemaking.

-----------------------------------------------------------------------

SUMMARY: 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.
    This Notice of Proposed Rulemaking proposes 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.
    The addition of a definition for the term ``positional isomer'' 
will assist legitimate research 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 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: Written comments must be postmarked, and electronic comments 
must be sent, on or before July 24, 2006.

ADDRESSES: To ensure proper handling of comments, please reference 
``Docket No. DEA-260P'' on all written and electronic correspondence. 
Written comments being sent 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 the DEA Headquarters, 
Attention: DEA Federal Register Representative/ODL, 2401 Jefferson-
Davis Highway, Alexandria, VA 22301. Comments may be directly sent to 
the DEA electronically by sending an electronic message to 
[email protected]. An electronic copy of this document is 
also available at the http://www.regulations.gov Web site. The DEA will 
accept attachments to electronic comments in Microsoft Word, 
WordPerfect, Adobe PDF, or Excel file formats only. The DEA will not 
accept any file format other than those specifically listed here.

FOR FURTHER INFORMATION CONTACT: Christine A. Sannerud, Ph.D., Chief, 
Drug and Chemical Evaluation Section, Office of Diversion Control, Drug 
Enforcement Administration,

[[Page 30098]]

Washington, DC 20537 at (202) 307-7183.

SUPPLEMENTARY INFORMATION:

Background

    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.
    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 proposing that a specific definition for ``positional 
isomer'' 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 Proposed Definition Is Needed

    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.
    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).
    The DEA is not proposing the addition of definitions for either 
optical or geometric isomers. The DEA believes that these terms are 
highly specific and are not subject to differing scientific 
interpretation.

Proposed 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 which 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

    The addition of a definition for the term ``positional isomer'' as 
it applies to 21 CFR 1308.11(d) will assist legitimate research 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

[[Page 30099]]

``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 Proposed 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.
    Title 21 CFR 1300.01(b)(21) is proposed to be revised to include a 
specific definition for the term ``positional isomer''. The proposed 
modification will specify that, as used in Sec.  1308.11(d), the term 
``positional isomer'' means any substance possessing the same molecular 
formula and core structure and has 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, would be 
within the 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 
(and 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 Proposed Definition

    The DEA understands that the proposed 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.

Request for Comments

    The proposed 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. The DEA welcomes input from all 
interested parties regarding the proposed definition of ``positional 
isomer.'' Prior to publication of a Final Rule, the DEA will consider 
all comments received. Comments must be submitted on or before July 24, 
2006.

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 proposed 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 
section 1(b). The DEA has determined that this is not a significant 
regulatory action. Therefore, this action has not 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 
$117,000,000 or more 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.

Small Business Regulatory Enforcement Fairness Act of 1996

    This rule is not a major rule as defined by section 804 of the 
Small Business Regulatory Enforcement Fairness Act of 1996. 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.

    For the reasons set out above, 21 CFR part 1300 is proposed to be 
amended as follows:

PART 1300--DEFINITIONS [AMENDED]

    1. The authority citation for part 1300 continues to read as 
follows:

    Authority: 21 U.S.C. 802, 871(b), 951, 958(f).

    2. Sec.  1300.01 is proposed to be amended by revising paragraph 
(b)(21) to read as follows:

[[Page 30100]]

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: May 17, 2006.
Michele M. Leonhart,
Deputy Administrator.
 [FR Doc. E6-7979 Filed 5-24-06; 8:45 am]
BILLING CODE 4410-09-P