Paper comments: Paper comments that duplicate the electronic submission are not necessary and are discouraged. Should you wish to mail a paper comment in lieu of an electronic comment, it should be sent via regular or express mail to: Drug Enforcement Administration, Attn: DEA Federal Register Representative/DPW, Morrissette Drive, Springfield, Virginia .
If you are looking for more details, kindly visit Mandybio International.
Electronic comments: The Drug Enforcement Administration (DEA) encourages all comments be submitted electronically through the Federal eRulemaking Portal, which provides the ability to type short comments directly into the comment field on the web page or to attach a file for lengthier comments. Please go to http://www.regulations.gov/&#; and follow the online instructions at that site for submitting comments. Upon completion of your submission, you will receive a Comment Tracking Number for your comment. Please be aware that submitted comments are not instantaneously available for public view on http://www.regulations.gov/&#; . If you have received a Comment Tracking Number, your comment has been successfully submitted and there is no need to resubmit the same comment.
The Drug Enforcement Administration is proposing to designate 3,4-MDP-2-P methyl glycidate (PMK glycidate), including its optical and geometric isomers; 3,4-MDP-2-P methyl glycidic acid (PMK glycidic acid), including its salts, optical and geometric isomers, and salts of isomers; and alpha -phenylacetoacetamide (APAA), including its optical isomers, as list I chemicals under the Controlled Substances Act (CSA). PMK glycidate and PMK glycidic acid are used in and are important to the manufacture of the schedule I controlled substance 3,4-methylenedioxymethamphetamine (MDMA) and other &#;ecstasy&#;-type substances. APAA is used in and is important to the manufacture of the schedule II controlled substances amphetamine and methamphetamine. If finalized, this action would subject handlers (manufacturers, distributors, importers, and exporters) of PMK glycidate, PMK glycidic acid, and APAA to the chemical regulatory provisions of the CSA and its implementing regulations. This action does not propose the establishment of a threshold for domestic and international transactions of these chemicals. As such, all transactions involving any of these chemicals, regardless of size, would be regulated. In addition, this action proposes that chemical mixtures containing any of these three chemicals would not be exempt from regulatory requirements at any concentration. Therefore, all transactions of chemical mixtures containing any quantity of PMK glycidate, PMK glycidic acid, or APAA would be regulated.
Please note that all comments received are considered part of the public record. They will, unless reasonable cause is given, be made available by the Drug Enforcement Administration (DEA) for public inspection online at http://www.regulations.gov. Such information includes personal identifying information (such as name, address, etc.) voluntarily submitted by the commenter. The Freedom of Information Act applies to all comments received. If you want to submit personal identifying information (such as your name, address, etc.) as part of your comment, but do not want it to be made publicly available, you must include the phrase &#;PERSONAL IDENTIFYING INFORMATION&#; in the first paragraph of your comment. You must also place ( print page ) all of the personal identifying information you do not want publicly available in the first paragraph of your comment and identify what information you want redacted.
If you want to submit confidential business information as part of your comment, but do not want it to be made publicly available, you must include the phrase &#;CONFIDENTIAL BUSINESS INFORMATION&#; in the first paragraph of your comment. You must also prominently identify confidential business information to be redacted within the comment.
Comments containing personal identifying information and confidential business information identified as directed above will generally be made publicly available in redacted form. If a comment has so much confidential business information or personal identifying information that it cannot be effectively redacted, all or part of that comment may not be made publicly available. Comments posted to http://www.regulations.gov may include any personal identifying information (such as name, address, and number) included in the text of your electronic submission that is not identified as directed above as confidential.
An electronic copy of this document and supplemental information to this proposed rule are available at http://www.regulations.gov for easy reference.
The Controlled Substances Act (CSA) gives the Attorney General the authority to specify, by regulation, a chemical as a &#;list I chemical;&#; this term refers to a chemical that is used in manufacturing a controlled substance in violation of subchapter I (Control and Enforcement) of the CSA and is important to the manufacture of the controlled substance.[ ] Pursuant to 28 CFR 0.100(b), the Attorney General has delegated his authority to so designate list I chemicals to the Administrator of DEA (Administrator). CSA regulations permit the Administrator to add a substance as a listed chemical by publishing a final rule in the Federal Register following the publication of a notice of proposed rulemaking that has provided at least 30 days for public comments.[ ] The current list of all list I chemicals is available in 21 CFR .02(a).
In addition, the United States is a Party to the United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances ( Convention), December 20, , U.N.T.S. 95. Under Article 12 of the Convention, when the United States receives notification that a chemical has been added to Table I or Table II (tables annexed to such Convention), the United States must take measures it deems appropriate to monitor the manufacture and distribution of that chemical within the United States and to prevent its diversion, including measures related to international trade.
With the growing problem of illicit drug production, the issue of precursor chemical control has gained global attention. International efforts to prevent the illicit production of controlled substances and international control of precursors have made significant progress with this problem. Article 12 of the Convention established International controls on precursors. This Convention established two categories of controlled illicit drug precursor substances: Table I and Table II.[ ] Two international entities have played a crucial role in this effort: The United Nations Commission on Narcotic Drugs (CND) and the International Narcotics Control Board (INCB).
In response to domestic and international controls on precursors to the schedule I substance 3,4-methylenedioxymethamphetamine (MDMA), and schedule II substances amphetamine and methamphetamine, clandestine laboratory operators have continued to explore alternate methods to produce these illicit drugs, including the development of their own immediate precursors (&#;designer precursors&#;) and diversion of other precursors (pre-precursors) to produce these designer precursors. These clandestine laboratory operators often use 3,4-MDP-2-P methyl glycidate (PMK glycidate) and 3,4-MDP-2-P methyl glycidic acid (PMK glycidic acid) as precursors to MDMA, and other &#;ecstasy&#;-type substances, and alpha -phenylacetoacetamide (APAA) as a precursor to amphetamine and methamphetamine.
&#;Precursor chemicals&#; are generally defined as chemical substances that become incorporated, at the molecular level, into a final product (including a controlled substance); it is a building block used to manufacture the final product/controlled substance. PMK glycidate and PMK glycidic acid are building blocks for the manufacture of the schedule I controlled substance MDMA, while APAA serves as a building block for the manufacture of the schedule II substance Phenyl-2-propanone (P2P), and subsequent final manufacture of the schedule II substances amphetamine and methamphetamine. All these chemicals meet the definition of list I chemicals since they are important to the manufacture of these controlled substances.
In a letter dated May 23, , the Secretary-General of the United Nations, in accordance with Article 12, paragraph 6 of the Convention, informed the United States Secretary of State that the CND voted to place the chemicals PMK glycidate (and all stereoisomers), PMK glycidic acid (and all stereoisomers), and APAA (and all optical isomers) in Table I of the Convention (CND Decisions 62/10, 62/11, and 62/12, respectively) at its 62nd Session on March 19, . As a Party to the Convention, the United States is obligated to control these substances pursuant to Article 12 of the Convention, as described in the above Legal Authority section. By designating PMK glycidate (and its optical and geometric isomers), PMK glycidic acid (and its salts, optical and geometric isomers, and salts of isomers), and APAA (and its optical isomers) as list I chemicals, the United States will fulfill its obligations under the Convention.[ ]
PMK glycidate, PMK glycidic acid, and APAA are close chemical relatives of controlled list I precursor 3,4 methylenedioxyphenyl-2-propanone (3,4-MDP-2-P), and have been made specifically to circumvent existing precursor controls. DEA has not identified any known legitimate uses for these chemicals, other than possible research purposes. The first two substances, PMK glycidate and PMK glycidic acid, are closely related in chemical structure to precursors of MDMA (schedule I) and other &#;ecstasy&#;-type substances in schedule I. APAA is a precursor of schedule II controlled substances amphetamine and methamphetamine. All three chemicals are used for the illicit manufacture of two precursors listed in Table I of the Convention (3,4-MDP-2-P and 1-phenyl-2-propanone (P-2-P)). For years, countries have reported the illicit trafficking and use of these chemicals in manufacturing controlled substances, ( print page ) with increasing frequency and amounts reported in recent years.[ ]
In making its assessments pursuant to Article 12, paragraph 4, of the Convention, the CND found that there was no known legitimate manufacture of, and trade in, any of the three substances, and that their use was limited in small amounts to research, development, and laboratory analytical purposes. The inclusion of these substances in Table I would require Governments, as parties to the Convention, to establish pre-export notifications as a means of monitoring shipments entering their territories. Therefore, the CND voted to include PMK glycidate (all four stereoisomers), PMK glycidic acid (all four stereoisomers), and APAA (including its optical isomers) in Table I of the Convention.
For the reasons discussed above, the Acting Administrator of DEA finds that PMK glycidate, PMK glycidic acid, and APAA are used in the manufacture of a controlled substance in violation of the CSA, and are important to the manufacture of these controlled substances. Therefore, the Acting Administrator proposes the designation of PMK glycidate, PMK glycidic acid, and APAA as list I chemicals.
If finalized, handlers (manufacturers, distributors, importers, and exporters) of these chemicals would become subject to the chemical regulatory provisions of the CSA, including 21 CFR parts , , , and . Since even a small amount of these chemicals can potentially yield a significant amount of controlled substances, this action does not propose the establishment of a threshold for domestic, import, or export transactions in accordance with the provisions of 21 CFR .04(g). Rather, DEA is proposing that all transactions, regardless of size, will be regulated transactions as defined in 21 CFR .02(b). As such, if finalized, all PMK glycidate, PMK glycidic acid, and APAA transactions will be subject to recordkeeping, reporting, import and export controls, and other CSA chemical regulatory requirements. In addition, each regulated bulk manufacturer must submit manufacturing, inventory, and use data to DEA's Diversion Control Division, Drug and Chemical Evaluation section on an annual basis, in accordance with 21 CFR .05(d).
This rulemaking also proposes that chemical mixtures containing any of these three chemicals are subject to regulatory requirements at any concentration unless a manufacturer submits to DEA an application for exemption of a chemical mixture, DEA accepts the application for filing, and DEA exempts the chemical mixture in accordance with 21 CFR .13 (Exemption of chemical mixtures; application). Since even a small amount of these three chemicals can potentially yield a significant amount of controlled substances, DEA believes that regulation of chemical mixtures containing any amount of these three chemicals is necessary to prevent their illicit extraction, isolation, and use. Therefore, all chemical mixtures containing any quantity of these three chemicals would be subject to CSA control. This rule proposes modification of the &#;Table of Concentration Limits&#; in 21 CFR .12(c) to reflect the fact that chemical mixtures containing any amount of these three chemicals are subject to CSA chemical control provisions.
DEA has implemented an application process to exempt certain chemical mixtures from the requirements of the CSA and its implementing regulations.[ ] Manufacturers may submit an application for exemption for those mixtures that do not meet the criteria set forth in 21 CFR .12(d) for an automatic exemption. Pursuant to 21 CFR .12(a), DEA may grant an exemption of a chemical mixture, by publishing a final rule in the Federal Register , if DEA determines that: (1) The mixture is formulated in such a way that it cannot be easily used in the illicit production of a controlled substance, and (2) the listed chemical or chemicals cannot be readily recovered.
If finalized as proposed, the designation of these three chemicals as list I chemicals will subject handlers (manufacturers, distributors, importers, and exporters) and proposed handlers to all of the regulatory controls and administrative, civil, and criminal actions applicable to the manufacture, distribution, importation, and exportation of a list I chemical. Upon publication of a final rule, persons potentially handling these three chemicals, including regulated chemical mixtures containing any of these three chemicals, would be required to comply with the following list I chemical regulations:
1. Registration. Any person who handles (manufactures, distributes, imports, or exports), or proposes to engage in such handling of, any of these three chemicals or a chemical mixture containing any of these three chemicals must obtain a registration pursuant to 21 U.S.C. 822, 823, 957, and 958. Regulations describing registration for list I chemical handlers are set forth in 21 CFR part . DEA regulations require separate registrations for manufacturing, distributing, importing, and exporting of any of these three chemicals.[ ] Further, a separate registration is required for each principal place of business at one general physical location where list I chemicals are manufactured, distributed, imported, or exported by a person.[ ]
DEA notes that under the CSA, &#;warehousemen&#; are not required to register and may lawfully possess list I chemicals, if the possession of those chemicals is in the usual course of business or employment.[ ] Under DEA implementing regulations, the warehouse in question must receive the list I chemical from a DEA registrant, shall only distribute the list I chemical back to the DEA registrant, and registered location from which it was received.[ ] A warehouse that distributes list I chemicals to persons other than the registrant and registered location from which they were obtained is conducting distribution activities and is required to register as such.
Upon publication of a final rule, any person manufacturing, distributing, importing, or exporting any of these three chemicals or a chemical mixture containing any of these three chemicals will become subject to the registration requirement under the CSA. DEA recognizes, however, that it is not possible for persons subject to the registration requirement to immediately complete and submit an application for ( print page ) registration and for DEA to immediately issue registrations for those activities. Therefore, to allow continued legitimate commerce in these three chemicals, DEA is proposing to establish in 21 CFR .09 a temporary exemption from the registration requirement for persons desiring to engage in activities with any of these three chemicals, provided that DEA receives a properly completed application for registration on or before 30 days after publication of a final rule implementing regulations regarding these three chemicals. The temporary exemption for such persons will remain in effect until DEA takes final action on their application for registration or application for exemption of a chemical mixture.
The temporary exemption applies solely to the registration requirement; all other chemical control requirements, including recordkeeping and reporting, would become effective on the effective date of the final rule. Therefore, all transactions of these three chemicals and chemical mixtures containing any of these three chemicals will be regulated while an application for registration or exemption is pending. This is necessary because failing to regulate these transactions could result in increased diversion of chemicals desirable to drug traffickers.
Additionally, the temporary exemption does not suspend applicable federal criminal laws relating to these three chemicals, nor does it supersede State or local laws or regulations. All handlers of any of these three chemicals must comply with applicable State and local requirements in addition to the CSA regulatory controls.
2. Records and Reports. Every DEA registrant would be required to maintain records and submit reports to DEA with respect to these three chemicals pursuant to 21 U.S.C. 830(a) and (b)(1) and (2) and in accordance with 21 CFR .04 and .05. Pursuant to 21 CFR .04(a), a record must be made and maintained for two years after the date of a transaction involving a listed chemical, provided the transaction is a regulated transaction.
Each regulated bulk manufacturer of a listed chemical is required to submit manufacturing, inventory, and use data on an annual basis.[ ] Existing standard industry reports containing the required information will be acceptable, provided the information is separate or readily retrievable from the report.
The CSA and its implementing regulations require that each regulated person must report to DEA any regulated transaction involving an extraordinary quantity of a listed chemical, an uncommon method of payment or delivery, or any other circumstance that the regulated person believes may indicate that the listed chemical will be used in violation of subchapter I of the CSA. In addition, regulated persons must report any proposed regulated transaction with a person whose description or other identifying characteristics DEA has previously furnished to the regulated person, any unusual or excessive loss or disappearance of a listed chemical under the control of the regulated person, and any in-transit loss in which the regulated person is the supplier.[ ]
3. Importation and Exportation. All importation and exportation of these three chemicals would need to be in compliance with 21 U.S.C. 957, 958, and 971 and in accordance with 21 CFR part .
4. Security. All applicants and registrants would be required to provide effective controls against theft and diversion in accordance with 21 CFR .71-.73.
5. Administrative Inspection. Places, including factories, warehouses, or other establishments and conveyances, where registrants or other regulated persons may lawfully hold, manufacture, distribute, or otherwise dispose of a list I chemical or where records relating to those activities are maintained, are controlled premises as defined in 21 U.S.C. 880(a) and 21 CFR .02(c). The CSA allows for administrative inspections of these controlled premises as provided in 21 CFR part , subpart A. 21 U.S.C. 88).
6. Liability. Any activity involving these three chemicals not authorized by, or in violation of, the CSA would be unlawful, and may subject the person to administrative, civil, and/or criminal action.
This proposed rule was developed in accordance with the principles of Executive Orders (E.O.) , , and . E.O. directs agencies to assess all costs and benefits of available regulatory alternatives and, if regulation is necessary, to select regulatory approaches that maximize net benefits (including potential economic, environmental, public health, and safety effects; distributive impacts; and equity). E.O. is supplemental to and reaffirms the principles, structures, and definitions governing regulatory review as established in E.O. . E.O. classifies a &#;significant regulatory action,&#; requiring review by the Office of Management and Budget (OMB), as any regulatory action that is likely to result in a rule that may: (1) Have an annual effect on the economy of $100 million or more or adversely affect in a material way the economy, a sector of the economy, productivity, competition, jobs, the environment, public health or safety, or State, local, or tribal governments or communities; (2) create a serious inconsistency or otherwise interfere with an action taken or planned by another agency; (3) materially alter the budgetary impact of entitlements, grants, user fees, or loan programs or the rights and obligations of recipients thereof; or (4) raise novel legal or policy issues arising out of legal mandates, the President's priorities, or the principles set forth in the E.O. DEA has determined that this proposed rule is not a &#;significant regulatory action&#; under E.O. , section 3(f).
E.O. requires an agency, unless prohibited by law, to identify at least two existing regulations to be repealed when the agency publicly proposes for notice and comment or otherwise promulgates a new regulation.[ ] In furtherance of this requirement, E.O. requires that the new incremental costs associated with new regulations, to the extent permitted by law, be offset by the elimination of existing costs associated with at least two prior regulations.[ ] According to guidance provided by OMB, the requirements of E.O. only apply to each new &#;significant regulatory action that . . . imposes costs.&#;&#;[ ] This proposed rule is not expected to be an E.O. regulatory action because this proposed rule is not significant under E.O. .
If finalized as proposed, PMK glycidate, PMK glycidic acid, and APAA will be subject to all of the regulatory controls and administrative, civil, and criminal sanctions applicable to the manufacture, distribution, importing, and exporting of list I chemicals. The first two chemicals, PMK glycidate and PMK glycidic acid, are closely related in chemical structure to precursors of MDMA and other &#;ecstasy&#;-type substances, as discussed in the above background section. APAA is a ( print page ) precursor of amphetamine and methamphetamine. All three chemicals are highly suitable for the illicit manufacture of precursors listed in Table I of the Convention (3,4-methylenedioxyphenyl-2-propanone (3,4-MDP-2-P) and 1-phenyl-2-propanone (P-2-P)). As noted earlier, incidents of illicit manufacture and tracking of these three chemicals have been reported for many years to the INCB, with an increase in the frequency and amounts reported in recent years.
In making its assessment pursuant to Article 12, paragraph 4 of the Convention, the CND found that there was no known legitimate manufacture of and trade in any of the three chemicals and that their use was limited, in small amounts, to research, development, laboratory, and analytical purposes. DEA also searched information in the public domain for legitimate uses of these three chemicals, and likewise, did not identify any known legitimate use for any of these chemicals, other than possibly for research purposes. DEA evaluated the costs and benefits of this proposed action.
DEA cannot rule out the possibility that minimal quantities of PMK glycidate, PMK glycidic, or APAA are used for the manufacturing of legitimate pharmaceutical substances. DEA welcomes any public comment on these quantities and their economic significance.
As stated above, the only use for PMK glycidate and PMK glycidic acid is as intermediaries for the manufacturing of MDMA and other &#;ecstasy&#;-type substances. Similarly, the only use for APAA is as a precursor for amphetamine and methamphetamine. Any manufacturer, distributor, importer, or exporter of any of these three chemicals for legitimate pharmaceutical commerce, if they exist at all, would incur costs if this proposed rule were finalized. The primary costs associated with this proposed rule are the annual registration fees ($3,047 for manufacturers and $1,523 for distributors, importers, and exporters). Additionally, any manufacturer that uses any of these three chemicals for legitimate pharmaceutical purposes is likely to already be registered with DEA and have all security and other handling processes in place, resulting in minimal cost.
DEA has identified ten domestic suppliers of one or more of these chemicals, PMK glycidate, PMK glycidic acid, and APAA; nine of these suppliers are not currently registered with DEA to handle list I chemicals. The amount of these three chemicals distributed by these suppliers is unknown. It is common for chemical distributors to have items on their catalog while not actually having any material level of sales. Based on the discussion above, DEA believes any quantity of sales from these distributors for legitimate pharmaceutical purposes is minimal. If this proposed rule is finalized, suppliers for the legitimate use of PMK glycidate, PMK glycidic acid, and APAA are expected to choose the least-cost option, and stop selling the minimal quantities, if any, of PMK glycidate, PMK glycidic acid, and APAA, rather than incur the registration cost. Therefore, DEA estimates that the cost of foregone sales is minimal; and thus, the cost of this proposed rule is minimal. DEA welcomes any public comment regarding this estimate.
This analysis excludes consideration of any economic impact to those businesses that facilitate the manufacturing and distribution of PMK glycidate, PMK glycidic acid, or APAA for the illicit production of amphetamine, methamphetamine, MDMA, or other &#;ecstasy&#;-type substances.
Controlling PMK glycidate, PMK glycidic acid, and APAA is expected to prevent, curtail, and limit the unlawful manufacture and distribution of amphetamine, methamphetamine, and MDMA and other &#;ecstasy&#;-type substances. This action is also expected to assist in the prevention of possible theft or diversion of PMK glycidate, PMK glycidic acid, and APAA from any legitimate firms. DEA also believes control is necessary to prevent unscrupulous chemists from synthesizing PMK glycidate, PMK glycidic acid, and APAA and selling it (as an unregulated material) through the internet and other channels to individuals who may wish to acquire unregulated intermediary chemicals for the purpose of manufacturing illicit amphetamine, methamphetamine, or MDMA or other &#;ecstasy&#;-type substances.
In summary, DEA conducted a qualitative analysis of costs and benefits. DEA believes this proposed action, if finalized, will minimize the diversion of PMK glycidate, PMK glycidic acid, and APAA. DEA believes the market for PMK glycidate, PMK glycidic acid, and APAA for the legitimate pharmaceutical purposes is minimal. Thus, any potential cost resulting from this regulation is minimal. Therefore, the estimated economic impact of this proposed rule is less than $100 million in any given year.
This proposed regulation meets the applicable standards set forth in sections 3(a) and 3(b)(2) of E.O. to eliminate drafting errors and ambiguity, minimize litigation, provide a clear legal standard for affected conduct, and promote simplification and burden reduction.
This proposed rulemaking does not have federalism implications warranting the application of E.O. . The proposed rule does not have substantial direct effects on the states, on the relationship between the national government and the states, or the distribution of power and responsibilities among the various levels of government.
This proposed rule does not have tribal implications warranting the application of E.O. . It does not have substantial direct effects on one or more Indian tribes, on the relationship between the Federal Government and Indian tribes, or on the distribution of power and responsibilities between the Federal Government and Indian tribes.
The Acting Administrator, in accordance with the RFA,[ ] has reviewed this proposed rule, and by approving, it certifies that it will not have a significant economic impact on a substantial number of small entities. As discussed above, if finalized as proposed, PMK glycidate, PMK glycidic acid, and APAA will be subject to all of the regulatory controls and administrative, civil, and criminal sanctions applicable to the manufacture, distribution, importation, and exportation of list I chemicals. PMK glycidate and PMK glycidic acid are closely related in chemical structure to precursors of MDMA and other &#;ecstasy&#;-type substances. APAA is a precursor of amphetamine and methamphetamine. All three chemicals are highly suitable for the illicit manufacture of precursors listed in Table I of the Convention (3,4-methylenedioxyphenyl-2-propanone (3,4-MDP-2-P) and 1-phenyl-2-propanone (P-2-P)). DEA has not ( print page ) identified any legitimate industrial use for PMK glycidate, PMK glycidic acid, or APAA, other than as intermediary chemicals in the production of amphetamine, methamphetamine, and MDMA or other &#;ecstasy&#;-type substances. Therefore, DEA believes the vast majority, if not all, of PMK glycidate, PMK glycidic acid, and APAA is used for the illicit manufacturing of amphetamine, methamphetamine, and MDMA or other &#;ecstasy&#;-type substances. The primary costs associated with this proposed rule are the annual registration fees ($3,047 for manufacturers and $1,523 for distributors, importers, and exporters). Additionally, any manufacturer that uses PMK glycidate, PMK glycidic acid, or APAA for legitimate pharmaceutical purposes is likely to be already registered with DEA and have all security and other handling processes in place, resulting in minimal cost.
DEA has identified ten domestic suppliers of one or more of the chemicals, PMK glycidate, PMK glycidic acid, and APAA; nine of these suppliers are currently not registered with DEA to handle list I chemicals. All nine non-registered domestic suppliers are affected, and all nine (94.5 percent, based on Small Business Administration size standard for chemical distributors and Statistics of U.S. Businesses data) are estimated to be small entities. The quantity of these three chemicals distributed by these suppliers is unknown. It is common for chemical distributors to have items on their catalog while not actually having any material level of sales. Based on the discussion above, DEA believes any quantity of sales from these distributors for legitimate pharmaceutical purposes is minimal. DEA estimates that this proposed rule, if promulgated, will not have a significant economic impact on a substantial number of small entities. DEA welcomes any public comment regarding this estimate.
Unfunded Mandates Reform Act of
In accordance with the Unfunded Mandates Reform Act (UMRA), 2 U.S.C. et seq., DEA has determined and certifies that this proposed rule would not result in any Federal mandate that may result &#;in the expenditure by State, local, and tribal governments, in the aggregate, or by the private sector, of $100 million or more (adjusted annually for inflation) in any 1 year . . . .&#; Therefore, neither a Small Government Agency Plan nor any other action is required under the UMRA.
The proposed action does not impose a new collection of information requirement under the Paperwork Reduction Act, 44 U.S.C. -. This proposed action would not impose recordkeeping or reporting requirements on State or local governments, individuals, businesses, or organizations. An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number.
Accordingly, for the reasons set forth in the preamble, DEA proposes to amend 21 CFR part as follows:
1. The authority citation for part continues to read as follows:
2. In §&#;.02 add paragraphs (a)(34) through (36) to read as follows:
§&#;.02Substances covered.
*
*
*
*
*
(a) * * *
(34) 3,4-MDP-2-P methyl glycidate (PMK glycidate) and its optical and geometric isomers
(35) 3,4-MDP-2-P methyl glycidic acid (PMK glycidic acid) and its salts, optical and geometric isomers, and salts of isomers
(36) alpha -phenylacetoacetamide (APAA) and its optical isomers
3. In §&#;.04:
a. Redesignate paragraphs (g)(1)(vii) through (xiii) as paragraphs (g)(1)(x) through (xvi), respectively;
b. Redesignate paragraphs (g)(1)(i) through (vi) as paragraphs (g)(1)(ii) through (vii), respectively; and
c. Add new paragraphs (g)(1)(i), (viii), and (ix).
The additions read as follows:
§&#;.04Maintenance of records.
*
*
*
*
*
For more information, please visit pmk ethyl glycidate.
(g) * * *
(1) * * *
(i) alpha -phenylacetoacetamide (APAA) and its optical isomers
*
*
*
*
*
(viii) 3,4-MDP-2-P methyl glycidate (PMK glycidate) and its optical and geometric isomers
(ix) 3,4-MDP-2-P methyl glycidic acid (PMK glycidic acid) and its salts, optical and geometric isomers, and salts of isomers
*
*
*
*
*
4. Amend §&#;.09 by adding paragraph (q) to read as follows:
§&#;.09Temporary exemption from registration.
*
*
*
*
*
(q)(1) Each person required under 21 U.S.C. 822 and 957 to obtain a registration to manufacture, distribute, import, or export regulated forms of 3,4-MDP-2-P methyl glycidate (PMK glycidate), 3,4-MDP-2-P methyl glycidate (PMK glycidate), and alpha -phenylacetoacetamide (APAA), including regulated chemical mixtures pursuant to §&#;.12, is temporarily exempted from the registration requirement, provided that DEA receives a properly completed application for registration or application for exemption for a chemical mixture containing regulated forms of 3,4-MDP-2-P methyl glycidate (PMK glycidate), 3,4-MDP-2-P methyl glycidic acid (PMK glycidic acid), or alpha -phenylacetoacetamide (APAA) pursuant to §&#;.13 on or before (30 days after publication of a rule implementing regulations regarding these three chemicals). 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 the Act and parts , , , and of this chapter remain in full force and effect.
(2) Any person who manufactures, distributes, imports or exports a chemical mixture containing regulated forms of 3,4-MDP-2-P methyl glycidate (PMK glycidate), 3,4-MDP-2-P methyl glycidic acid (PMK glycidic acid), or alpha -phenylacetoacetamide (APAA) 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 those persons whose applications for exemption are denied, 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 been denied. The temporary exemption for such persons will remain in effect until DEA takes final action on their registration application.
5. Amend §&#;.12(c) by adding in alphabetical order entries for 3,4-MDP- ( print page ) 2-P methyl glycidate (PMK glycidate), 3,4-MDP-2-P methyl glycidic acid (PMK glycidic acid), and alpha -phenylacetoacetamide (APAA) in the table &#;Table of Concentration Limits&#; to read as follows:
§&#;.12Exempt chemical mixtures.
*
*
*
*
*
(c) * * *
Table of Concentration Limits
&#; DEA chemical code No. Concentration Special conditions &#; *&#;&#;&#;&#;&#;&#;&#;&#;&#;*&#;&#;&#;&#;&#;&#;&#;&#;&#;*&#;&#;&#;&#;&#;&#;&#;&#;&#;*&#;&#;&#;&#;&#;&#;&#;&#;&#;*&#;&#;&#;&#;&#;&#;&#;&#;&#;*&#;&#;&#;&#;&#;&#;&#;&#;&#;* 3,4-MDP-2-P methyl glycidate (PMK glycidate) and its optical and geometric isomers Not exempt at any concentration Chemical mixtures containing any amount of this chemical are not exempt. 3,4-MDP-2-P methyl glycidic acid (PMK glycidic acid) and its salts, optical and geometric isomers, and salts of isomers Not exempt at any concentration Chemical mixtures containing any amount of this chemical are not exempt. alpha -phenylacetoacetamide (APAA) and its optical isomers Not exempt at any concentration Chemical mixtures containing any amount of this chemical are not exempt. &#; *&#;&#;&#;&#;&#;&#;&#;&#;&#;*&#;&#;&#;&#;&#;&#;&#;&#;&#;*&#;&#;&#;&#;&#;&#;&#;&#;&#;*&#;&#;&#;&#;&#;&#;&#;&#;&#;*&#;&#;&#;&#;&#;&#;&#;&#;&#;*&#;&#;&#;&#;&#;&#;&#;&#;&#;*
*
*
*
*
*
Timothy J. Shea,
Acting Administrator.
This resource is part of EU Drug Market: Methamphetamine &#; In-depth analysis by the EMCDDA and Europol.
Last update: 6 May
There are many ways to make methamphetamine, and each has its own risks and advantages. In Europe, two main methods exist, classified according to the chemicals used as starting materials, known as precursors. One method is based on ephedrine or pseudoephedrine which can be imported in bulk powder or extracted from medicinal products or even from ephedra plants. This method is hazardous and difficult to scale up; in Europe, it is mostly used in small- to medium-scale &#;kitchen&#; laboratories in and around Czechia, where precursors extracted from medicines are typically used. This method produces the potent d-isomer form of methamphetamine (d-methamphetamine (1). The other method uses BMK (also called benzyl methyl ketone, or phenyl-2-propanone, &#;P-2-P&#;), an oil that can be imported to the EU or made in Europe from chemicals known as designer precursors (also called pre-precursors). This method is more amenable to scaling up and is therefore suitable for use in industrial-scale laboratories, as has been observed in the Netherlands and Belgium. Its main disadvantage is that the resulting product is a 50:50 mixture of the d- and l-isomers, the l-methamphetamine being a less desirable product. This means an additional step is needed at the end of the synthesis to separate and purify the potent (hence preferred) illicit product: d-methamphetamine. Techniques to perform this separation have been used in illicit production laboratories in Mexico since at least (INCB, ) and more recently in the Netherlands and Belgium. Recent data also shows that European BMK-based laboratories have further increased the efficiency and output of production by recycling the unwanted l-methamphetamine to obtain more d-methamphetamine for each litre of BMK used (see Section Recycling unwanted by-product: a game-changer in methamphetamine production).
BMK has limited legitimate uses; in Europe it is mostly used to produce amphetamine, and increasingly, for the production of methamphetamine. BMK may be imported to the EU but it is more often produced locally from pre-precursors.
BMK methods typically involve the catalytic reduction (reductive amination) of an intermediate formed between BMK and methylamine. In Europe, there are two main techniques: (1) reductive amination uses the &#;aluminium amalgam method&#;; (2) the &#;high pressure method&#; is the same technique used to produce MDMA in Europe, the only difference being the starting material (the precursor), where BMK yields methamphetamine and PMK (piperonal methyl ketone, also known as methylenedioxyphenyl-2-propanone, &#;MDP-2-P&#;) yields MDMA.
In , seven EU Member States seized close to 5 600 litres of BMK, most of which (75 %) was reported by the Netherlands (4 200 litres). These are globally relevant amounts, with only Mexico reporting larger seizures in (11 000 litres seized), according to the INCB ().
Importantly, these values need to be considered in the context of the close to 35 tonnes of various pre-precursor chemicals seized in the EU in , which could be used to produce significant additional amounts of BMK, often in dedicated &#;conversion&#; laboratories. These pre-precursors include APAAN, glycidic derivatives of BMK, APAA and MAPA, all of which were successively introduced in the market as soon as legal controls were applied to their predecessors (see Figure Quantity of designer precursors for the synthesis of BMK seized in Europe). In , five Member States reported combined pre-precursor seizures of over 1 tonne. These were Belgium (12 tonnes), Germany (almost 8 tonnes), Hungary (7 tonnes), the Netherlands (less than 7 tonnes) and France (1 tonne). Whenever the origin of the seizures was outside the EU (68 % of the quantity seized), the consignments originated in China (including Hong Kong) and were typically misdeclared as chemical industrial products or other commercial goods.
In Europe, the rapid replacement of pre-precursors has been particularly evident since , when information exchange between international authorities was enhanced, leading to more effective precursor diversion control worldwide (EMCDDA, a). To avoid disruptions to the steady supply of precursors for illicit laboratories, producers quickly changed from the scheduled precursor BMK to APAAN, which then became one of the most seized pre-precursors from to . The scheduling of APAAN in led to the appearance of glycidic derivatives of BMK, quickly followed by APAA which took the lead in seizures from to . APAA was scheduled in , leading to the emergence and prevalence of MAPA in seizures during and . MAPA was then scheduled in late , and in that same year, EAPA (the ethyl analogue of MAPA) was seized for the first time in Europe. These data illustrate the ingenuity and adaptability of synthetic drug producers: the declining seizures of one pre-precursor are accompanied by the concomitant rise of another (see Figure Quantity of designer precursors for the synthesis of BMK seized in Europe).
Quantity of designer precursors for the synthesis of BMK seized in Europe, -Source table. Quantity of designer precursors for the synthesis of BMK seized in Europe, -
(
Kilograms
) Year MAPA APAA Glycidic derivatives of BMK APAAN 0 0 0 0 75 0 0 0 0 0 202 0 597 489 66 292 24The availability of BMK and BMK precursor alternatives in Europe, although important, only provides an indication of the overall capacity to produce amphetamine-based stimulants. However, the manufacture of methamphetamine requires additional production steps, the chemicals required for which can provide more information on the trends and scale of methamphetamine production in Europe.
BMK methods produce 50:50 mixtures of d- and l-isomers of methamphetamine (a racemic mixture) (Maxwell and Brecht, ). To extract d-methamphetamine from the mixture, it can be treated with an &#;optically pure&#; substance, and typically tartaric acid is used. This process is called &#;resolution&#; and reduces the overall yields of the synthesis to 50 %. This type of separation process is well known to Mexican synthetic drug producers, and tartaric acid has been seized in association with drug production in Mexico since at least (INCB, ).
In , almost 18 tonnes of tartaric acid was seized in Europe, (see Figure Quantity of tartaric acid seized in Europe). Theoretically, this would be enough to separate up to 36 tonnes of a racemic mixture of methamphetamine, resulting in a potential yield of up to 18 tonnes of d-methamphetamine.
These data confirm what has been found in illicit laboratories: that large quantities of methamphetamine are being produced in Europe in industrial-scale laboratories, using methods associated with Mexican methamphetamine producers.
Large seizures in of the methamphetamine-specific adulterant, methylsulfonylmethane, provide additional evidence of an increase in the processing of the drug in Europe that year. Methylsulfonylmethane (also known as methyl sulphone or dimethyl sulphone) is ideally suited to adulterate crystal methamphetamine because, during processing as the mixture recrystallises, it resembles pure crystal methamphetamine (EMCDDA and Europol, ). Seizures of methylsulphfonylmethane were rarely reported in the European database of precursors until , when the Netherlands reported four seizures totalling more than 2 tonnes; the large majority of which appears to have been made in a single seizure at an illicit laboratory.
Quantity of tartaric acid seized in Europe, &#;Source table. Quantity of tartaric acid seized in Europe, &#; (
Kilograms
) Year Belgium Germany Netherlands 63 875 154 623Previously, when the d-methamphetamine was separated using tartaric acid, the leftover material containing the l-isomer was regarded as an unwanted by-product to be discarded. Illustrating the continuous drive to improve efficiency and profits, illicit drug producers in Europe have introduced new methods to reconvert these discarded solutions back to a racemic 50:50 mixture of d- and l-methamphetamine, from which the d-methamphetamine can be separated using tartaric acid. These recycling procedures explain the record quantities of tartaric acid seized in Europe (see Figure Quantity of tartaric acid seized in Europe).
This process can be repeated several times: each time a fraction with the unwanted l-methamphetamine is produced, it can be reconverted (&#;racemised&#;) back to a mixture and the d-isomer separated until the waste cannot be further recycled. The process, called &#;RRR&#; (resolution-racemisation-recycling) (see Figure Processing of methamphetamine: resolution-racemisation-recycling), is a standard technique used in the pharmaceutical industry to increase production yields of medicines where only one isomer is pharmaceutically active (Astleford and Weigel, ). The RRR technique increases the yield of d-methamphetamine from BMK from 50 % to 75 % after one iteration, up to 87.5 % on the second iteration and 93.75 % by the third. The racemisation of the discarded solutions of l-methamphetamine is triggered using small amounts of a chemical such as AIBN (or another radical initiator) and a source of thiyl radicals (for example methyl thioglycolate, thioglycolic acid or dimyristyl peroxydicarbonate) (Escoubet et al., ; Yerande et al., ). AIBN has a low decomposition temperature, can easily ignite and its use presents a risk of explosion (National Center for Biotechnology Information, ).
Data reported to the European Commission indicates that in , 327 kilograms of AIBN, 525 kilograms of methyl thioglycolate, 248 kilograms of dimyristyl peroxydicarbonate and 2.5 litres of thioglycolic acid were seized in Europe. Partial data available for indicate seizures of 19 kilograms of AIBN, 90 kilograms of methyl thioglycolate, 139 kilograms of dimyristyl peroxydicarbonate and 20 litres of thioglycolic acid. All seizures occurred in the Netherlands and some were seized during the dismantling of illicit laboratories. Information reported by Dutch police to the EMCDDA indicates that at least one shipment of 13 kilograms of AIBN in originated in Mexico. As well as indicating the level of sophistication involved, bearing in mind that these reagents are required in small amounts (relative to the quantity of methamphetamine being treated), the quantities seized provide further evidence of the scale of methamphetamine production using BMK methods in Europe. They also show that combining the expertise of Mexican and Dutch drug producers and applying techniques from the pharmaceutical industry has maximised production efficiency.
Processing of methamphetamine: resolution-racemisation-recyclingUntil the advent of methamphetamine production based on BMK in the Netherlands and Belgium, European production of methamphetamine was mostly based on ephedrine or pseudoephedrine precursors; this is still the method typically found in small- to medium-sized laboratories in Czechia and neighbouring countries (most often using the &#;Nagai method&#;) and also involves the use of iodine and red phosphorous. When in powder form, these precursors are regulated at international and EU level, but they can also be obtained from over-the-counter medicinal products, which takes them out of the scope of precursor legislation (Council of the European Union, ), and presents challenges for enforcement. Restrictions have been put in place to tackle multiple purchases of the medicines at national level in Czechia and more recently Germany and Poland, but the lack of a harmonised approach at EU level often results in trafficking from countries with less stringent regulations to those where production occurs (or from outside the EU).
Ephedrine and pseudoephedrine can be chemically reduced using a variety of agents (2). Starting from ephedrine or pseudoephedrine has the advantage that the product obtained is d-methamphetamine, so there is no need to go through the RRR process. However, there are several factors that make this method difficult to scale up, including challenges in obtaining the bulk precursor or the strictly controlled medicines; extracting sufficient quantities of precursor from the medicines; safely controlling the chemical reactions to avoid explosions; and obtaining good enough yields after the purification and crystallisation processes. Hence, production via this method in Europe usually operates at capacities less than 50 grams (see Section Methamphetamine production facilities dismantled in the EU).
In , 38 seizures amounting to 8 kilograms of ephedrine and 107 seizures amounting to 234 kilograms of pseudoephedrine were reported by 12 Member States. Poland seized close to 70 % of the EU total, which included pseudoephedrine preparations, i.e. medicines (mostly shipped from the United Kingdom) and pseudoephedrine raw material, i.e. powder (reported as intra-EU trade). In , two thefts of pseudoephedrine (raw material and hydrochloride) amounting to 536 kilograms were reported by Germany, indicating that attempts to obtain pseudoephedrine for methamphetamine production go beyond trafficking and diversion.
In , seizures of other chemicals associated with the production of methamphetamine from ephedrine and pseudoephedrine, including red phosphorus, iodine, hydriodic acid, hypophosphorous acid and phosphorous acid, were typically modest and made at local level. Action to prevent the diversion of red phosphorus for methamphetamine production was taken in , when it was added to the EU regulations governing drug precursors (Council of the European Union, ). In some incidents, seizures were made in small methamphetamine laboratories in Czechia, but also in Germany, Italy, the Netherlands, Austria and Slovakia.
The available data on the number of seizures and the quantities of ephedrine, pseudoephedrine and associated chemicals seized in Europe did not change significantly from to , beyond the expected natural fluctuations (see Figure Quantities of ephedrine and pseudoephedrine seized in Europe), despite the large increases in seizures of methamphetamine in Europe. This supports the view that the current &#;creeping&#; market expansion is not related to the ephedrine/pseudoephedrine method, but rather the BMK methods.
Quantities of ephedrine and pseudoephedrine seized in Europe, -Source table. Quantities of ephedrine and pseudoephedrine seized in Europe, - (
Kilograms
) Quantity Ephedrine Pseudoephedrine 10 210 65 48 32 41 164 241 56 49 8 234Synthetic drug production poses a number of possible hazards. In the last few years, a number of fatalities have been recorded in synthetic drug production laboratories in the Netherlands and Belgium due to fires or explosions (van den Berg, ) or suffocation from carbon monoxide or other toxic fumes caused by the production process (Steenberghe, ). A scientific review of cases of exposure to chemicals in illicit drug laboratories linked the exposure not only to mild or moderate respiratory, ocular and dermal effects, but also to severe symptoms and fatalities (Koppen et al., ). As with all synthetic drug production, the manufacture of methamphetamine does not just pose hazards to those involved in production; it also leads to the generation of chemical waste products, which are typically dumped away from the production site (but within a reasonable radius). Given the location of many laboratories, this can mean in a neighbouring country, such as Belgium, Germany or the Netherlands. Europol information also suggests that people that supply clean chemicals to illicit laboratories may collect the waste for disposal at locations far from the production zone. Such techniques can frustrate efforts to identify production sites and present collateral risks for the environment and people involved.
One kilogram of methamphetamine produced using the red phosphorus method generates 5-6 kilograms of waste (Europol, ). Waste is also produced when methamphetamine is produced from BMK, and when BMK is produced from designer precursors. This results in environmental damage, health risks and high clean-up costs. A variety of methods are used to dispose of the large quantities of chemical waste created during synthetic drug production. For example, the waste may be simply poured down the sink or toilet, although this is likely to be rare, as the waste can be corrosive or so viscous that it would block the drains. If chemical waste is disposed of in this way, it may affect the quality of drinking water or adversely affect municipal wastewater treatment plants (Schoenmakers et al., ). More commonly, members of the public report containers of waste dumped in the countryside, and there have also been instances where waste has been found buried underground. Waste can also be left in abandoned property or loaded into stolen vans or lorry trailers, which may then be set on fire to conceal forensic evidence. More elaborate methods have been found, including the use of modified vans that pump waste onto road surfaces. Six dumping sites specifically related to methamphetamine were reported in two in Belgium, related to dumping of equipment, and four in the Netherlands. Since methamphetamine in those countries is mainly produced using BMK, it is not always possible to determine whether the dump sites are related to amphetamine or methamphetamine production.
Knowledge of the mechanisms and extent of environmental damage related to synthetic drug production is fragmented and this is an under-researched area. While there are stand-alone studies on specific impacts, a more comprehensive and complete assessment of the environmental impact of synthetic drug production has not yet been done. Researchers in Czechia found that the presence of methamphetamine in wastewater leads to indications of dependence and behavioural changes among fish, disturbing mating habits and potentially impacting the aquatic ecosystem (Horký et al., ). A better understanding is needed of the impact of methamphetamine production waste and methamphetamine residues on biodiversity and the environment.
Consult the list of references used in this resource.
Want more information on cas 16 7? Feel free to contact us.