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Proposed Rule

Definition of “Positional Isomer” as It Pertains to the Control of Schedule I Controlled Substances

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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 dea.diversion.policy@usdoj.gov. 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.

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FOR FURTHER INFORMATION CONTACT:

Christine A. Sannerud, Ph.D., Chief, Drug and Chemical Evaluation Section, Office of Diversion Control, Drug Enforcement Administration, Start Printed Page 30098Washington, DC 20537 at (202) 307-7183.

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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 §§ 1308.11(d) and 1308.12(b)(4) of this chapter. As used in § 1308.11(d) of this chapter, the term “isomer” means the optical, positional, or geometric isomer. As used in § 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 §§ 1308.11(d) and 1308.12(b)(4) of this chapter. As used in § 1308.11(d) of this chapter, the term “isomer” means the optical, positional, or geometric isomer. As used in § 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 Start Printed 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 § 1308.11(d) and § 1308.12(b)(4) of this chapter. As used in § 1308.11(d) of this chapter, the term “isomer” means any optical, positional, or geometric isomer. As used in § 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 § 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 §§ 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.

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List of Subjects in 21 CFR Part 1300

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

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PART 1300—DEFINITIONS [AMENDED]

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

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

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

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Definitions relating to controlled substances.
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(b) * * *

(21)(i) The term isomer means the optical isomer, except as used in § 1308.11(d) and § 1308.12(b)(4) of this chapter. As used in § 1308.11(d) of this chapter, the term “isomer” means any optical, positional, or geometric isomer. As used in § 1308.12(b)(4) of this chapter, the term “isomer” means any optical or geometric isomer.

(ii) As used in § 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.

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Dated: May 17, 2006.

Michele M. Leonhart,

Deputy Administrator.

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[FR Doc. E6-7979 Filed 5-24-06; 8:45 am]

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