Source: https://www.federalregister.gov/documents/2003/05/01/03-10565/exemption-of-chemical-mixtures-containing-the-list-i-chemicals-ephedrine-n-methylephedrine
Timestamp: 2018-07-17 16:16:37
Document Index: 564692212

Matched Legal Cases: ['§\u20091310', 'art 1309', '§\u20091310', '§\u20091310', '§\u20091310', 'arts 1309', '§\u20091310', '§\u20091310', '§\u20091310', '§\u20091310']

Federal Register :: Exemption of Chemical Mixtures Containing the List I Chemicals Ephedrine, N-Methylephedrine, N-Methylpseudoephedrine, Norpseudoephedrine, Phenylpropanolamine, and Pseudoephedrine
A Rule by the Drug Enforcement Administration on 05/01/2003
Effective June 2, 2003. Persons seeking registration must apply on or before June 30, 2003 in order to continue their business pending final action by DEA on their application.
23195-23206 (12 pages)
Docket No. DEA-137F1
Request for Exemption of Multiple Ingredient Dietary Supplements or Products With Less Than Five Percent Total Ephedrine/Pseudoephedrine
https://www.federalregister.gov/d/03-10565 https://www.federalregister.gov/d/03-10565
On September 16, 1998, the Drug Enforcement Administration (DEA) published a Notice of Proposed Rulemaking (NPRM) to implement provisions of the Controlled Substances Act (CSA) pertaining to the regulation of chemical mixtures which contain any of 34 listed chemicals. The NPRM was published to implement CSA requirements that only those chemical mixtures identified by regulation be exempt from applicable regulatory controls.
Frank Sapienza, Chief, Drug & Chemical Evaluation Section, Office of Diversion Control, Drug Enforcement Administration, Washington, DC 20537, telephone (202) 307-7183.
DEA originally proposed a concentration level of two percent for chemical mixtures containing ephedrine and/or pseudoephedrine. However, based on the comments received from the NPRM (63 FR 49506, Sept. 16, 1998), DEA has determined that a two percent concentration level would create significant regulatory burdens for the affected industry. Therefore, based on comments received, DEA has determined that a five percent concentration level will permit access to these products, while ensuring that these products are unlikely to be subject to diversion for the illegal manufacture of methamphetamine.
This final rule also establishes an exemption for the category of products consisting of unaltered harvested plant material, which DEA believes are not subject to diversion regardless of the concentration of the List I chemical in the product. Finally, this rule provides for a process whereby a manufacturer of a product which would otherwise be subject to regulation may request an exemption for that specific product. This process will allow chemical mixtures not automatically exempt by the concentration limit to be considered for exempt status under the CSA. Start Printed Page 23196
The Chemical Diversion and Trafficking Act of 1988 (CDTA) created a definition of “chemical mixture” (21 U.S.C. 802(40)), and exempted chemical mixtures from regulatory coverage. The Domestic Chemical Diversion Control Act of 1993 (DCDCA), enacted in April of 1994, created a provision dealing with the exemption of chemical mixtures. Chemical mixtures are defined as “a combination of two or more chemical substances, at least one of which is not a list I chemical or a list II chemical, except that such term does not include any combination of a list I chemical or a list II chemical with another chemical that is present solely as an impurity.”
Prior to the enactment of the DCDCA, the term “regulated transaction” was defined to exclude “any transaction in a chemical mixture'' (21 U.S.C. 802(39)(A)(v)). Therefore, transactions involving all chemical mixtures (including dietary supplements) were exempt from recordkeeping, registration and other chemical regulatory control requirements of the CSA.
The DCDCA amended the CSA (21 U.S.C. 802(39)(A)(v)) to limit the application of the above stated exemption and provided the Attorney General with the authority to exempt a chemical mixture containing a listed chemical if it is “formulated in such a way that it cannot be easily used in the illicit production of a controlled substance” and “the listed chemical or chemicals contained in the mixture cannot be readily recovered.” Until regulations which delineate criteria and procedures for exempting specific chemical mixtures are finalized, DEA has treated all chemical mixtures as being exempt from the chemical regulatory requirements of the CSA. (Note that OTC and prescription drug products are not considered chemical mixtures and are addressed separately under 21 U.S.C. 802(39)(A)(iv)).
Some chemical mixtures can be and have been used by traffickers in the illicit manufacture of controlled substances. This exemption provided traffickers with an unregulated source for obtaining these chemicals. To address these problems, the DCDCA amended the exemption to provide that only those chemical mixtures specified by regulation would be exempt from the definition of “regulated transaction'.
The DEA proposed that each chemical be assigned a concentration limit that, if found at or below the limit, will cause the mixture to be treated as a nonregulated chemical. This quantitative approach to identifying regulated mixtures is considered necessary due to the complexity of chemical-based commodities and the huge variety of products. These criteria are expected to exempt the vast majority of chemical mixtures containing listed chemicals. The NPRM included the proposed creation of a “Table of Start Printed Page 23197Concentration Limits,” in 21 CFR 1310.12. This table lists the concentration limits for each listed chemical.
On February 28, 2003 the U.S. Department of Health and Human Services (HHS) and Food and Drug Administration (FDA) announced a series of actions designed to protect the public from potentially serious risks from the use of dietary supplement products containing ephedra. The announcement cites new evidence in the medical literature and in adverse event reports, of heightened concerns that dietary supplements containing ephedra may represent a “significant and unreasonable risk of illness and injury.” DEA recognizes that determinations regarding the safety of such dietary supplement products are the purview of HHS/FDA. This rule does not address the issue of safety or human consumption of such products.
While the September 16, 1998 Notice of Proposed Rulemaking “Exemption of Chemical Mixtures” (63 FR 49506) pertained to the regulation of chemical mixtures which contained any of 34 listed chemicals, this rulemaking finalizes only those portions of the NPRM pertaining to six specific chemicals: ephedrine, N-methylephedrine, N-methylpseudoephedrine, norpseudoephedrine, phenylpropanolamine, and pseudoephedrine. These chemicals are precursors to methamphetamine and related substances.
This final rule establishes a concentration limit for each of these six listed chemicals. If the concentration of the listed chemical is at or below the limit, then the mixture will be automatically exempted and therefore treated as a nonregulated chemical mixture. These concentration limits are provided in the “Table of Concentration Limits,” in 21 CFR 1310.12. The weight of the free base will be used to determine the concentration of a listed chemical if it is a salt. A mixture is exempt if the concentration of the listed chemical or chemicals is less than or equal to the percentages and other conditions described in the “Table of Concentration Limits.”
This final rulemaking also establishes an exemption for a category of chemical mixtures which contain ephedrine, N-methylephedrine, N-methylpseudoephedrine, norpseudoephedrine, phenylpropanolamine, and/or pseudoephedrine. While these mixtures may have higher concentration limits than provided above, the DEA believes they are not a likely source of diversion due to their inherent composition. Therefore, this rule also establishes an Start Printed Page 23198exemption for the category of products consisting of harvested plant material.
Prior to publication of the notice of proposed rulemaking “Exemption of Chemical Mixtures” (63 FR 49506) on September 16, 1998, the DEA attempted to learn as much as possible about the affected industry. The DEA first established contact with industry shortly after withdrawal of the regulations regarding the exemption of Start Printed Page 23199chemical mixtures proposed by DEA on October 13, 1994 (59 FR 51888). That portion of the proposal was withdrawn on December 9, 1994 (59 FR 63738) in response to industry concerns. DEA met with representatives from associations (and affiliated members) representing chemical manufacturers, the paints and coating industry, flavor and fragrance manufacturers, chemical distributors, the dietary supplements industry and others. These different groups expressed unique concerns that the DEA attempted to address within the notice of proposed rulemaking (63 FR 49506).
This Rulemaking will affect only persons who manufacture, distribute, import, or export chemical formulations containing the List I chemicals ephedrine, N-methylephedrine, N-methylpseudoephedrine, norpseudoephedrine, phenylpropanolamine, and/or pseudoephedrine. End users, including those who manufacture a regulated mixture and convert it to a nonregulated form in an on-site manufacturing process, are not affected. Of those persons whose mixtures are regulated, only those distributions above the established threshold quantity for the listed chemical(s) are regarded as regulated transactions (as specified in 21 CFR 1310.04). Since no threshold has been established for ephedrine, all transactions in regulated chemical mixtures containing ephedrine will be regulated transactions. The threshold for regulated chemical mixtures containing N-methylephedrine, N-methylpseudoephedrine, norpseudoephedrine, phenylpropanolamine, and pseudoephedrine are found in 21 CFR 1310.04(f)(1). This Final Rule will not affect the regulatory status for chemical mixtures containing the remaining listed chemicals.
This is an appropriate decision at this time, for most dietary supplements are not formulated in such a way to be easily used in the illicit manufacture of a controlled substance and are therefore not likely to be diverted. This will exempt the majority of these chemical mixtures from regulatory controls. Taking this information into account, DEA is implementing a concentration limit of five percent (total ephedrine/pseudoephedrine). This should exempt those dietary supplements which are not likely to be sources of precursor material for clandestine laboratories. By taking this action, DEA is endeavoring to permit public access to these chemical mixtures while ensuring that they are not subject to diversion. Based on the comments DEA received, as well as discussions with members of the affected industry, DEA believes that dietary and nutritional supplements will not be adversely affected by this rulemaking, and that the public will continue to have full access to these products.
DEA proposed new regulations regarding the exemption of chemical mixtures by publishing an NPRM on September 16, 1998, entitled “Exemption of Chemical Mixtures” (63 FR 49506). The comment period, which was twice extended, closed on April 16, 1999. Comments discussed in this Final Rule will be limited to those related to the listed chemicals being addressed in this Final Rule. Two comments addressed ephedrine and pseudoephedrine only in relation to dietary supplement products. There were no comments on N-methylephedrine, N-methylpseudoephedrine, norpseudoephedrine, or phenylpropanolamine.
One comment requested that DEA automatically exempt multiple ingredient dietary supplement products containing ephedrine alkaloids or, alternatively, increase the concentration limit for ephedrine from two to five percent. The comment also requested that the capsule weight be considered in determining automatic exemption.
Some formulators add additional ephedrine to standardize a product. This practice is used to assure uniformity between batches of raw Start Printed Page 23200material obtained from natural sources. However, this method may also be used to formulate supplements that have an unnaturally high level of ephedrine or other alkaloid. This is sometimes referred to as “spiking.” Both standardization and spiking imply that the product is not “all natural” and contains pharmaceutical grade ephedrine, or ephedrine hydrochloride. Ephedrine hydrochloride is the most common form of ephedrine used by clandestine laboratory operators to make methamphetamine.
As stated on one of the labels provided to DEA, the ephedra supplement may be standardized to obtain an amount of ephedrine at least equal to that found in OTC drug products. As noted above, standardization is achieved by using a synthetic form of ephedrine, ephedrine hydrochloride, which may be useful to traffickers. That form is more easily separated from other ingredients due to its affinity for water. DEA determined that exempting dietary supplements or “multiple ingredient” dietary supplements would create a loophole for the diversion of methamphetamine precursor. A supplement can be “standardized” to contain up to 25 mg of ephedrine with minimal additional ingredients that results in a high weight ratio of ephedrine and be legally marketed as a dietary supplement. Therefore, DEA has decided not to exempt dietary supplements as a category.
One commentor stated that methamphetamine cannot be produced from their dietary supplement products. The commentor sponsored an experiment to prove this assertion. The dietary supplement used in the experiment was calculated to contain one percent ephedrine by laboratory analysis. The laboratory report refers to a common “street method” for manufacturing methamphetamine. However, the sponsored experiment using this supplement was not successful in producing methamphetamine.
The commentor acknowledged that significant problems existed with some manufacturers “spiking” products with synthetically produced ephedrine. Although the commentor states that they believe this practice has been mostly corrected, DEA must consider the likelihood of such practices. Voluntary compliance with standards of an organization or any special interest group can not prevent unscrupulous persons from distributing mixtures desired by traffickers. Without a concentration limit, products can be marketed as dietary supplements that are “spiked” to contain high levels of ephedrine with minimal additional ingredients. These formulations can be legally marketed as dietary supplements and be desirable to traffickers.
Three persons commented on the application process as being limited because it requires a separate application for each mixture. They suggest that the application process should account for a group or family of mixtures and allow for variation, sometimes necessary to meet customer needs, without having to reapply for exemption. Start Printed Page 23201
DEA intended to allow group exemption by application. A group is defined as those formulations having identical function and containing the same listed chemical(s). The Notice of Proposed Rulemaking states (63 FR 49511) “The application may be submitted for a single mixture or a group of mixtures containing the same listed chemical at equal concentration with variations in the concentration of the other non-listed chemicals in the mixture. Consideration will also be given to applications for mixtures in which the concentration of the listed chemical varies without regard to the specific concentrations of the other non-listed chemicals in the mixture. In either group, variation of the concentration of any chemical within the mixture that will result in a change in the function of the mixture will disqualify the mixture from the group.”
DEA will address below the shortcoming in the proposed § 1310.13 that does not clearly establish group exemption. In addition, DEA shall establish that a single formulation may be granted an exemption while allowing variation in the formulation without the need to reapply. This is in anticipation that reformulation may be necessary to meet a customer's needs. Variation may be for listed and non-listed chemicals.
DEA must be informed if a qualitative change, not indicated on the original application, removes non-listed chemical(s) from a formulation exempt under a group. This is necessary to prevent mixtures being altered from an unusable state, as evaluated in the application, to a mixture that can be used by traffickers. If such a change (i.e., removal of non-listed chemical(s) from the formulation) renders the mixture valuable to traffickers, DEA can remove the exemption for that member of the group. DEA must be informed of such a change; however, a new application will not be necessary. DEA will either add the new formulation to the group or deny exempt status for that particular formulation. Section 1310.13 will be modified to reflect this and other conditions mentioned above.
Three commentors suggested that a 21-day deadline be established to determine whether a mixture is exempt by the application process. One person suggested that a 5-day deadline be imposed for approval of the application. A time frame was requested so manufacturers could establish internal compliance procedures before shipments are made.
While DEA will attempt to expedite the review of each application, it is not practical to establish a time limit for determining whether a mixture or a mixture group is exempt. The time to determine the status of an individual application is dependent on several variables that can not be controlled. Factors include the number of applications received, the number of mixtures contained in an application, the possible need to obtain additional technical information from the applicant, the possible need to obtain additional internal technical information on chemicals in the mixture and to analyze all factors. These and other factors make a time limit impractical.
A chemical mixture (other than the category of products consisting of unaltered harvested plant material) that contains ephedrine, N-methylephedrine, N-methylpseudoephedrine, norpseudoephedrine, phenylpropanolamine, or pseudoephedrine above the concentration limit as defined in the “Table of Concentration Limits” will be treated as a List I chemical. Transactions that meet or exceed the cumulative monthly threshold for the listed chemical shall be regulated transactions. Persons interested in handling a regulated mixture must comply with the following:
Registration. Any person who distributes, imports or exports a regulated mixture, or proposes to engage in such activities, or is a broker or trader in an international transaction (as defined in 21 U.S.C. 802(42)), with Start Printed Page 23202respect to a regulated mixture containing a List I chemical, shall obtain a registration pursuant to the CSA (21 U.S.C. 822). Regulations describing registration for list I handlers are set forth in 21 CFR part 1309.
Any person whose application for exemption is subsequently denied by DEA must obtain a registration with DEA. A temporary exemption from the registration requirement will also be provided for these persons, provided that DEA receives a properly completed application for registration on or before 30 days following the date of official DEA notification that the application for exemption has not been approved. The temporary exemption for such persons will remain in effect until DEA takes final action on their registration application.
DEA, pursuant to 21 U.S.C. 802(39)(A)(v), is defining criteria for the exemption of chemical mixtures containing one or more of the List I chemicals ephedrine, N-methylephedrine, N-methylpseudoephedrine, norpseudoephedrine, phenylpropanolamine, and pseudoephedrine from regulatory control. To implement an exemption, a concentration limit is placed on each chemical, or combination of chemicals, which defines its regulatory status. In addition, an application process is established to exempt chemical mixtures, not automatically exempt by these provisions, from the regulatory process.
However, a comment received in response to the NPRM suggested that the percent concentration of ephedrine and pseudoephedrine be raised from two percent to five percent. The commentor states that it represents individual member companies with hundreds of thousands of independent distributors. One member company alone is said to have over 100,000 distributors. The commentor suspects that its members will be regulated if a two percent concentration limit is finalized. Registration costs for this number of new registrants would result in a significant regulatory action. Start Printed Page 23203
DEA is also finalizing in this Rulemaking a process by which manufacturers may request exemption from DEA for specific products. This process will allow chemical mixtures not automatically exempt by the concentration limit to be considered for exempt status under the CSA. This will ensure that certain chemical mixtures, including dietary supplements having formulations useless to traffickers, but not automatically exempt by provision, can be granted exempt status.
Therefore, in accordance with the Regulatory Flexibility Act (5 U.S.C. 605(b)), the Acting Administrator has reviewed this Final Rule and by approving it certifies that this regulation will not have a significant economic impact upon a substantial number of small entities.
Authority: 21 U.S.C. 802, 871(b), 951, 958(f). 2. Section 1300.02 is amended by revising paragraph (b)(28)(i)(E) to read as follows:
(E) Any transaction in a chemical mixture designated in § 1310.12 and § 1310.13 that the Administrator has exempted from regulation.
(e) Each person required by section 302 of the Act (21 U.S.C. 822) to obtain a registration to distribute, import, or export regulated chemical mixtures which contain ephedrine, N-methylephedrine, N-methylpseudoephedrine, norpseudoephedrine, phenylpropanolamine, and/or pseudoephedrine, pursuant to §§ 1310.12 and 1310.13, is temporarily exempted from the registration requirement, provided that DEA receives a proper application for registration or application for exemption on or before June 30, 2003. The exemption will remain in effect for each person who has made such application until the Administration has approved or denied that application. This exemption applies only to registration; all other chemical control requirements set forth in parts 1309, 1310, and 1313 of this chapter remain in full force and effect. Any person who distributes, imports or exports a chemical mixture whose application for exemption is subsequently denied by DEA must obtain a registration with DEA. A temporary exemption from the registration requirement will also be provided for these persons, provided that DEA receives a properly completed application for registration on or before 30 days following the date of official DEA notification that the application for Start Printed Page 23204exemption has not been approved. The temporary exemption for such persons will remain in effect until DEA takes final action on their registration application.
(b) No exemption granted pursuant to this § 1310.12 or § 1310.13 affects the criminal liability for illegal possession, distribution, exportation, or importation of listed chemicals contained in the exempt chemical mixture or the civil liability for unlawful acts related to exempt chemical mixtures, including distribution in violation of 21 U.S.C. 842(a)(11).
(c) Mixtures containing a listed chemical in concentrations equal to or less than those specified in the “Table of Concentration Limits” are designated as exempt chemical mixtures for the purpose set forth in this section. The concentration is determined for liquid-liquid mixtures by using the volume or weight and for mixtures containing solids or gasses by using the unit of weight.
Ephedrine, its salts, optical isomers, and salts of optical isomers 8113 5% by Weight, (weight includes capsule, if any) Concentration based on any combination of ephedrine, pseudoephedrine, and their salts, optical isomers and salts of optical isomers
N-Methylephedrine, its salts, optical isomers, and salts of optical isomers 8115 0.1% by Weight, (weight includes capsule, if any) Concentration based on any combination of N-methylephedrine, N-methylpseudoephedrine and their salts, optical isomers and salts of optical isomers
N-methylpseudoephedrine, its salts, optical isomers, and salts of optical isomers 8119 0.1% by Weight (weight includes capsule, if any) Concentration based on any combination of N-methylpseudoephedrine, N-methylephedrine, and their salts, optical isomers and salts of optical isomers
Norpseudoephedrine, its salts, optical isomers, and salts of optical isomers 8317 0.6% by Weight (weight includes capsule, if any) Concentration based on any combination of norpseudoephedrine, phenylpropanolamine and their salts, optical isomers and salts of optical isomers
Phenylpropanolamine, its salts, optical isomers, and salts of optical isomers 1225 0.6% by Weight (weight includes capsule, if any) Concentration based on any combination of phenylpropanolamine, norpseudoephedrine and their salts, optical isomers and salts of optical isomers
Pseudoephedrine, its salts, optical isomers, and salts of optical isomers 8112 5% by Weight, (weight includes capsule, if any) Concentration based on any combination of pseudoephedrine, ephedrine, and their salts, optical isomers and salts of optical isomers
5. A new § 1310.13 is added to read as follows:
(2) The listed chemical or chemicals contained in the chemical mixture cannot be readily recovered. Start Printed Page 23205
(b) Any manufacturer seeking an exemption for a chemical mixture, not exempt under § 1310.12, from the application of all or any part of the Act, may apply to the Administrator, Drug Enforcement Administration, Department of Justice, Washington, DC 20537.
(i) The following chemical mixtures, in the form and quantity listed in the application submitted (indicated as the “date” ) are designated as exempt chemical mixtures for the purposes set forth in this section and are exempted by the Administrator from application of sections 302, 303, 310, 1007, and 1008 of the Act (21 U.S.C. 822, 823, 830, 957 and 958):