[Federal Register Volume 72, Number 231 (Monday, December 3, 2007)]
[Rules and Regulations]
[Pages 67850-67852]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-23413]



[[Page 67850]]

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

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.

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

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]
BILLING CODE 4410-09-P