( f) Total production volume. The estimated maximum amount of the new microorganism intended to be manufactured or imported during the first year of production and the estimated maximum amount to be manufactured or imported during any consecutive 12 month period during the first 3 years of production. This estimate may be by weight or volume and should include an estimation of viability ( i. e., viable cells per unit volume or colony forming units per unit dry weight).

( g) Use information. A description of intended categories of use by function and application, the estimated percent of production volume devoted to each category of use, and the percent of the new microorganism in the formulation for each commercial or consumer use.

( h) Worker exposure and environmental release. ( 1) For sites controlled by the submitter: ( i) The identity of sites where the new microorganism will be manufactured, processed, or used. For purposes of this section, the site for a person who imports a new microorganism is the site of May 10, 2004 the operating unit within the person's organization which is directly responsible for importing the new microorganism and which controls the import transaction. The import site may in some cases be the organization's headquarters office in the United States. ( ii) A process description of each manufacture, processing, and use operation, which includes a diagram of the major unit operations and conversions, the identity and entry point of all feedstocks, and the identity of any possible points of release of the new microorganism from the process, including a description of all controls, including engineering controls, used to prevent such releases. ( iii) Worker exposure information, including worker activities, physical form of process streams which contain the new microorganism to which workers may be exposed, the number of workers, and the duration of activities. ( iv) Information on release of the new microorganism to the environment, including the quantity and media of release and type of control technology used. ( v) A narrative description of the intended transport of the new microorganism, including the means of transport, containment methods to be used during transport, and emergency containment procedures to be followed in case of accidental release. ( vi) Procedures for disposal of any articles, waste, clothing, or other equipment involved in the activity, including procedures for inactivation of the new microorganism, containment, disinfection, and disposal of contaminated items.

( 2) For sites not controlled by the submitter, a description of each type of processing and use operation involving the new microorganism, including identification of the estimated number of processing or use sites, situations in which worker exposure to and/ or environmental release of the new microorganism will occur, the number of workers exposed and the duration of exposure; procedures for transport of the new microorganism and for disposal, including procedures for inactivation of the new microorganism; and control measures which limit worker exposure and environmental release.

§ 725.160 Submission of health and environmental effects data.

( a) Test data on the new microorganism in the possession or control of the submitter. ( 1) Except as provided in § 725.25( h), and in addition to the information required by § 725.155( d)( 3), each MCAN must contain all test data in the submitter's possession or control which are related to the effects on health or the environment of any manufacture, processing, distribution in commerce, use, or disposal of the new microorganism or any microbial mixture or article containing the new microorganism, or any combination of such activities. This includes test data concerning the new microorganism in a pure culture or formulated form as used or as intended to be used in one of the activities listed above.

( 2) A full report or standard literature citation must be submitted for the following types of test data: ( i) Health effects data. ( ii) Ecological effects data. ( iii) Physical and chemical properties data. ( iv) Environmental fate characteristics. ( v) Monitoring data and other test data related to human exposure to or environmental release of the new microorganism. May 10, 2004 ( 3)( i) If the data do not appear in the open scientific literature, the submitter must provide a full report. A full report includes the experimental methods and materials, results, discussion and data analysis, conclusions, references, and the name and address of the laboratory that developed the data. ( ii) If the data appear in the open scientific literature, the submitter need only provide a standard literature citation. A standard literature citation includes author, title, periodical name, date of publication, volume, and page numbers.

( 4)( i) If a study, report, or test is incomplete when a person submits a MCAN, the submitter must identify the nature and purpose of the study; name and address of the laboratory developing the data; progress to date; types of data collected, significant preliminary results; and anticipated completion date. ( ii) If a test or experiment is completed before the MCAN review period ends, the person must submit the study, report, or test, as specified in paragraph ( a)( 3)( i) of this section, to the address listed in § 725.25( c) within 10 days of receiving it, but no later than 5 days before the end of the review period. If the test or experiment is completed during the last 5 days of the review period, the submitter must immediately inform its EPA contact for that submission by telephone.

( 5) For test data in the submitter's possession or control which are not listed in paragraph ( a)( 2) of this section, a person is not required to submit a complete report. The person must submit a summary of the data. If EPA so requests, the person must submit a full report within 10 days of the request, but no later than 5 days before the end of the review period.

( 6) All test data described under paragraph ( a) of this section are subject to these requirements, regardless of their age, quality, or results. ( b) Other data concerning the health and environmental effects of the new microorganism that are known to or reasonably ascertainable by the submitter. ( 1) Except as provided in § 725.25( h), and in addition to the information required by § 725.155( c)( 3), any person who submits a MCAN must describe the following data, including any data from a health and safety study of a microorganism, if the data are related to effects on health or the environment of any manufacture, processing, distribution in commerce, use, or disposal of the microorganism, of any microbial mixture or article containing the new microorganism, or of any combination of such activities:

( i) Any data, other than test data, in the submitter's possession or control. ( ii) Any data, including test data, which are not in the submitter's possession or control, but which are known to or reasonably ascertainable by the submitter. For the purposes of this section, data are known to or reasonably ascertainable by the submitter if the data are known to any of its employees or other agents who are associated with the research and development, test marketing, or commercial marketing of the microorganism.

( 2) Data that must be described include data concerning the new microorganism in a pure culture or formulated form as used or as intended to be used in one of the activities listed in paragraph ( b)( 1) of this section.

( 3) The description of data reported under paragraph ( b) of this section must include: ( i) If the data appear in the open scientific literature, a standard literature citation, which includes the author, title, periodical name, date of publication, volume, and pages. May 10, 2004 ( ii) If the data are not available in the open scientific literature, a description of the type of data and summary of the results, if available, and the names and addresses of persons the submitter believes may have possession or control of the data.

( 4) All data described in paragraph ( b) of this section are subject to these requirements, regardless of their age, quality, or results; and regardless of whether they are complete at the time the MCAN is submitted.

§ 725.170 EPA review of the MCAN.

General procedures for review of all submissions under this part are contained in § § 725.28 through 725.60. In addition, the following procedures apply to EPA review of MCANs submitted under this subpart:

( a) Length of the review period. The MCAN review period specified in section 5( a) of the Act runs for 90 days from the date the Document Control Officer for the Office of Pollution Prevention and Toxics receives a complete MCAN, or the date EPA determines the MCAN is complete under § 725.33, unless the Agency extends the period under section 5( c) of the Act and § 725.56.

( b) Notice of expiration of MCAN review period. ( 1) EPA will notify the submitter that the MCAN review period has expired or that EPA has completed its review of the MCAN. Expiration of the review period does not constitute EPA approval or certification of the new microorganism, and does not mean that EPA may not take regulatory action against the microorganism in the future. ( 2) After expiration of the MCAN review period, in the absence of regulatory action by EPA under section 5( e), 5( f), or 6( a) of the Act, the submitter may manufacture or import the microorganism even if the submitter has not received notice of expiration. ( 3) Early notification that EPA has completed its review does not permit commencement of manufacture or import prior to the expiration of the 90 day MCAN review period.

( c) No person submitting a MCAN in response to the requirements of this subpart may manufacture, import, or process a microorganism subject to this subpart until the review period, including all extensions and suspensions, has expired.

§ 725.190 Notice of commencement of manufacture or import.

( a) Applicability. Any person who commences the manufacture or import of a new microorganism for nonexempt, commercial purposes for which that person previously submitted a section 5( a) notice under this part must submit a notice of commencement ( NOC) of manufacture or import.

( b) When to report. ( 1) If manufacture or import for nonexempt, commercial purposes begins on or after May 27, 1997, the submitter must submit the NOC to EPA no later than 30 calendar days after the first day of such manufacture or import.

( 2) If manufacture or import for nonexempt, commercial purposes began or will begin before May 27, 1997, the submitter must submit the NOC by May 27, 1997. May 10, 2004 ( 3) Submission of an NOC prior to the commencement of manufacture or import is a violation of section 15 of the Act.

( c) Information to be reported. The NOC must contain the following information: Specific microorganism identity, MCAN number, and the date when manufacture or import commences. If the person claimed microorganism identity confidential in the MCAN, and wants the identity to be listed on the confidential Inventory, the claim must be reasserted and resubstantiated in accordance with § 725.85( b). Otherwise, EPA will list the specific microorganism identity on the public Inventory.

( d) Where to submit. NOCs should be submitted to the address listed in § 725.25( c).

Subpart E  Exemptions for Research and Development Activities § 725.200 Scope and purpose.

( a) This subpart describes exemptions from the reporting requirements under subpart D of this part for research and development activities involving microorganisms. ( b) In lieu of complying with subpart D of this part, persons described in § 725.205 may submit a TSCA Experimental Release Application ( TERA) for research and development activities involving microorganisms or otherwise comply with this subpart. ( c) Exemptions from part 725 are provided at § § 725.232, 725.234, and 725.238. ( d) Submission requirements specific for TERAs are described at § 725.250. ( e) Data requirements for TERAs are set forth in § § 725.255 and 725.260. ( f) EPA review procedures specific for TERAs are set forth in § § 725.270 and 725.288. ( g) Subparts A through C of this part apply to any submission under this subpart.

§ 725.205 Persons who may report under this subpart.

( a) Commercial research and development activities involving new microorganisms or significant new uses of microorganisms are subject to reporting under this part unless they qualify for an exemption under this part.

( b) Commercial purposes for research and development means that the activities are conducted with the purpose of obtaining an immediate or eventual commercial advantage for the researcher and would include:

( 1) All research and development activities which are funded directly, in whole or in part, by a commercial entity regardless of who is actually conducting the research. Indications that the research and development activities are funded directly, in whole or in part, may include, but are not limited to: ( i) Situations in which a commercial entity contracts directly with a university or researcher; or ( ii) Situations in which a commercial entity gives a conditional grant where the commercial entity holds patent rights, or establishes a joint venture where the commercial entity holds patent or licensing rights; or ( iii) Any other situation in which the commercial entity intends to obtain an immediate or eventual May 10, 2004 commercial advantage for the commercial entity and/ or the researcher.

( 2) Research and development activities that are not funded directly by a commercial entity, if the researcher intends to obtain an immediate or eventual commercial advantage. Indications that the researcher intends to obtain an immediate or eventual commercial advantage may include, but are not limited to: ( i) The research is directed toward developing a commercially viable improvement of a product already on the market; or ( ii) The researcher has sought or is seeking commercial funding for the purpose of developing a commercial application; or ( iii) The researcher or university has sought or is seeking a patent to protect a commercial application which the research is developing; or ( iv) Other evidence that the researcher is aware of a commercial application for the research and has directed the research toward developing that application.

( c) Certain research and development activities involving microorganisms subject to jurisdiction under the Act are exempt from reporting under this part. A person conducting research and development activities which meet the conditions for the exemptions described in § § 725.232, 725.234, or 725.238 is exempt from TERA reporting under this subpart.

( d) A microorganism is not exempt from reporting under subpart D of this part if any amount of the microorganism, including as part of a mixture, is processed, distributed in commerce, or used, for any commercial purpose other than research and development.

( e) Quantities of the inactivated microorganism, or mixtures or articles containing the inactivated microorganism, remaining after completion of research and development activities may be disposed of as a waste in accordance with applicable Federal, State, and local regulations.

( f) A person who manufactures, imports, or processes a microorganism solely for research and development is not required to comply with the requirements of this section if:

( 1) The person is manufacturing a microbial pesticide identified in § 172.45( c), or ( 2) The person is manufacturing a microbial pesticide for which an Experimental Use Permit is required, pursuant to § 172.3; or ( 3) The person is manufacturing a microbial pesticide for which a notification or an Experimental Use Permit is not required to be submitted.

§ 725.232 Activities subject to the jurisdiction of other Federal programs or agencies.

This part does not apply to any research and development activity that meets all of the following conditions.

( a) The microorganism is manufactured, imported, or processed solely for research and development activities. ( b) There is no intentional testing of a microorganism outside of a structure, as structure is defined in § 725.3. ( c)( 1) The person receives research funds from another Federal agency, and the funds are May 10, 2004 awarded on the condition that the research will be conducted in accordance with the relevant portions of the NIH Guidelines, or ( 2) A Federal agency or program otherwise imposes the legally binding requirement that the research is to be conducted in accordance with relevant portions of the NIH Guidelines.

§ 725.234 Activities conducted inside a structure.

A person who manufactures, imports, or processes a microorganism is not subject to the reporting requirements under subpart D of this part if all of the following conditions are met:

( a) The microorganism is manufactured, imported, or processed solely for research and development activities. ( b) The microorganism is used by, or directly under the supervision of, a technically qualified individual, as defined in § 725.3. The technically qualified individual must maintain documentation of the procedures selected to comply with paragraph ( d) of this section and must ensure that the procedures are used. ( c) There is no intentional testing of a microorganism outside of a structure, as structure is defined in § 725.3. ( d) Containment and/ or inactivation controls. ( 1) Selection and use of containment and/ or inactivation controls inside a structure for a particular microorganism shall take into account the following: ( i) Factors relevant to the organism's ability to survive in the environment. ( ii) Potential routes of release in air, solids and liquids; in or on waste materials and equipment; in or on people, including maintenance and custodial personnel; and in or on other organisms, such as insects and rodents.

( iii) Procedures for transfer of materials between facilities.

( 2) The technically qualified individual's selection of containment and/ or inactivation controls shall be approved and certified by an authorized official ( other than the TQI) of the institution that is conducting the test prior to the commencement of the test.

( 3) Records shall be developed and maintained describing the selection and use of containment and/ or inactivation controls, as specified in § 725.235( c). These records, which must be maintained at the location where the research and development activity is being conducted, shall be submitted to EPA upon written request and within the time frame specified in EPA's request.

( 4) Subsequent to EPA review of records in accordance with paragraph ( d)( 3) of this section, changes to the containment/ inactivation controls selected under paragraph ( d)( 1) of this section must be made upon EPA order. Failure to comply with EPA's order shall result in automatic loss of eligibility for an exemption under this section.

( e) The manufacturer, importer, or processor notifies all persons in its employ or to whom it directly distributes the microorganism, who are engaged in experimentation, research, or analysis on the microorganism, including the manufacture, processing, use, transport, storage, and disposal of the microorganism associated with research and development activities, of any risk to health, identified under § 725.235( a), which may be associated with the microorganism. The notification must be made in accordance with § 725.235( b). May 10, 2004 § 725.235 Conditions of exemption for activities conducted inside a structure.

( a) Determination of risks. To determine whether notification under § 725.234( e) is required, the manufacturer, importer, or processor must do one of the following:

( 1) For research conducted in accordance with the NIH Guidelines, the manufacturer, importer, or processor must meet the conditions laid out at IV B 4 d of the NIH Guidelines; or ( 2) For all other research conducted in accordance with § 725.234, the manufacturer, importer, or processor must review and evaluate the following information to determine whether there is reason to believe there is any risk to health which may be associated with the microorganism: ( i) Information in its possession or control concerning any significant adverse reaction of persons exposed to the microorganism which may reasonably be associated with such exposure. ( ii) Information provided to the manufacturer, importer, or processor by a supplier or any other person concerning a health risk believed to be associated with the microorganism. ( iii) Health and environmental effects data in its possession or control concerning the microorganism. ( iv) Information on health effects which accompanies any EPA rule or order issued under TSCA section 4, 5, or 6 of the Act that applies to the microorganism and of which the manufacturer, importer, or processor has knowledge.

( b) Notification to employees and others. ( 1) The manufacturer, importer, or processor must notify the persons identified in § 725.234( e) by means of a container labeling system, conspicuous placement of notices in areas where exposure may occur, written notification to each person potentially exposed, or any other method of notification which adequately informs persons of health risks which the manufacturer, importer, or processor has reason to believe may be associated with the microorganism, as determined under paragraph ( a) of this section.

( 2) If the manufacturer, importer, or processor distributes a microorganism manufactured, imported, or processed under this section to persons not in its employ, the manufacturer, importer, or processor must in written form: ( i) Notify those persons that the microorganism is to be used only for research and development purposes and the requirements of § 725.234 are to be met. ( ii) Provide the notice of health risks specified in paragraph ( b)( 1) of this section.

( 3) The adequacy of any notification under this section is the responsibility of the manufacturer, importer, or processor.

( c) Recordkeeping. ( 1) For research conducted in accordance with the NIH Guidelines, a person who manufactures, imports, or processes a microorganism under this section must retain the following records: ( i) Documentation that the NIH Guidelines have been adhered to. Such documentation shall include: ( A) For experiments subject to Institutional Biosafety Committee review, or notification simultaneous with initiation of the experiment, the information submitted for review or notification, along with standard laboratory records, shall satisfy the recordkeeping requirements specified in § 725.234( d)( 3). ( B) For experiments exempt from Institutional Biosafety Committee review or notification simultaneous with initiation of the experiment, documentation of the exemption, along with May 10, 2004 standard laboratory records, shall satisfy the recordkeeping requirement specified in § 725.234( d)( 3). ( ii) Documentation of how the following requirements are satisfied under the NIH Guidelines: ( A) Copies or citations to information reviewed and evaluated to determine the need to make any notification of risk. ( B) Documentation of the nature and method of notification of risk, including copies of any labels or written notices used. ( C) The names and addresses of any persons other than the manufacturer, importer, or processor to whom the substance is distributed, the identity of the microorganism, the amount distributed, and copies of the notifications required.

( 2) For all other research conducted in accordance with § 725.234, a person who manufacturers, imports, or processes a microorganism under this section, must maintain the following records: ( i) Records describing selection and use of containment and/ or inactivation controls required by § 725.234( d)( 3) and certification by an authorized official required by § 725.234( d)( 2) for each microorganism. ( ii) Copies or citations to information reviewed and evaluated under paragraph ( a) of this section to determine the need to make any notification of risk. ( iii) Documentation of the nature and method of notification under paragraph ( b)( 1) of this section, including copies of any labels or written notices used.

( iv) The names and addresses of any persons other than the manufacturer, importer, or processor to whom the substance is distributed, the identity of the microorganism, the amount distributed, and copies of the notifications required under paragraph ( b)( 2) of this section.

§ 725.238 Activities conducted outside a structure.

( a) Exemption. ( 1) Research and development activities involving intentional testing in the environment of certain microorganisms listed in § 725.239 may be conducted without prior review by EPA if all of the conditions of this section and § 725.239 are met. ( 2) The research and development activity involving a microorganism listed in § 725.239 must be conducted by, or directly under the supervision of, a technically qualified individual, as defined in § 725.3.

( b) Certification. To be eligible for the exemption under this section, a manufacturer or importer must submit to EPA prior to initiation of the activity a document signed by an authorized official containing the following information: ( 1) Name, address, and telephone number of the manufacturer or importer. ( 2) Location, estimated duration, and planned start date of the test. ( 3) Certification of the following: ( i) Compliance with the conditions of the exemption specified for the microorganism in § 725.239. ( ii) If state and/ or local authorities have been notified of the activity, evidence of notification.

( c) Recordkeeping. Persons who conduct research and development activities under this section must comply with the recordkeeping requirements of § 725.65 and retain documentation that supports their compliance with the requirements of this section and the specific requirements for the microorganism listed in § 725.239. May 10, 2004 § 725.239 Use of specific microorganisms in activities conducted outside a structure.

( a) Bradyrhizobium japonicum. To qualify for an exemption under this section, all of the following conditions must be met for a test involving Bradyrhizobium japonicum:

( 1) Characteristics of recipient microorganism. The recipient microorganism is limited to strains of Bradyrhizobium japonicum.

( 2) Modification of traits. ( i) The introduced genetic material must meet the criteria for poorly mobilizable listed in § 725.421( c). ( ii) The introduced genetic material must consist only of the following components: ( A) The structural gene( s) of interest, which have the following limitations: ( 1) For structural genes encoding marker sequences, the gene is limited to the aadH gene, which confers resistance to the antibiotics streptomycin and spectinomycin. ( 2) For traits other than antibiotic resistance, the structural gene must be limited to the genera Bradyrhizobium and Rhizobium. ( B) The regulatory sequences permitting the expression of solely the gene( s) of interest.

( C) Associated nucleotide sequences needed to move genetic material, including linkers, homopolymers, adaptors, transposons, insertion sequences, and restriction enzyme sites. ( D) The vector nucleotide sequences needed for vector transfer. ( E) The vector nucleotide sequences needed for vector maintenance.

( 3) Limitations on exposure. ( i) The test site area must be no more than 10 terrestrial acres. ( ii) The technically qualified individual must select appropriate methods to limit the dissemination of modified Bradyrhizobium japonicum.

( b) Rhizobium meliloti. To qualify for an exemption under this section, all of the following conditions must be met for a test involving Rhizobium meliloti:

( 1) Characteristics of recipient microorganism. The recipient microorganism is limited to strains of Rhizobium meliloti. ( 2) Modification of traits. ( i) The introduced genetic material must meet the criteria for poorly mobilizable listed in § 725.421( c) of this part. ( ii) The introduced genetic material must consist only of the following components: ( A) The structural gene( s) of interest, which have the following limitations: ( 1) For structural genes encoding marker sequences, the gene is limited to the aadH gene, which confers resistance to the antibiotics streptomycin and spectinomycin. ( 2) For traits other than antibiotic resistance, the structural gene must be limited to the genera Bradyrhizobium and Rhizobium. ( B) The regulatory sequences permitting the expression of solely the gene( s) of interest. ( C) Associated nucleotide sequences needed to move genetic material, including linkers, homopolymers, adaptors, transposons, insertion sequences, and restriction enzyme sites. ( D) The vector nucleotide sequences needed for vector transfer. ( E) The vector nucleotide sequences needed for vector maintenance.

( 3) Limitations on exposure. ( i) The test site area must be no more than 10 terrestrial acres. May 10, 2004 ( ii) The technically qualified individual must select appropriate methods to limit the dissemination of modified Rhizobium meliloti.

§ 725.250 Procedural requirements for the TERA.

General requirements for all submissions under this part are contained in subparts A through C of this part. In addition, the following requirements apply to TERAs submitted under this subpart:

( a) When to submit the TERA. Each person who is eligible to submit a TERA under this subpart must submit the TERA at least 60 calendar days before the person intends to initiate the proposed research and development activity.

( b) Contents of the TERA. Each person who submits a TERA under this subpart must provide the information and test data described in § § 725.255 and 725.260. In addition, the submitter must supply sufficient information to enable EPA to evaluate the effects of all activities for which approval is requested.

( c) A person may submit a TERA for one or more microorganisms and one or more research and development activities, including a research program.

( d) EPA will either approve the TERA, with or without conditions, or disapprove it under procedures established in this subpart.

( e) The manufacturer, importer, or processor who receives a TERA approval must comply with all terms of the approval, as well as conditions described in the TERA, and remains liable for compliance with all terms and conditions, regardless of who conducts the research and development activity. Any person conducting the research and development activity approved under the TERA must comply with all terms of the TERA approval, as well as the conditions described in the TERA.

( f) Recordkeeping. Persons submitting a TERA must comply with the recordkeeping requirements of § 725.65. In addition, the following requirements apply to TERAs:

( 1) Each person submitting a TERA under this part must retain documentation of information contained in the TERA for a period of 3 years from the date that the results of the study are submitted to the Agency.

( 2) Summaries of all data, conclusions, and reports resulting from the conduct of the research and development activity under the TERA must be submitted to the EPA address identified in § 725.25( c) within 1 year of the termination of the activity.

§ 725.255 Information to be included in the TERA.

( a) To review a TERA, EPA must have sufficient information to permit a reasoned evaluation of the health and environmental effects of the planned test in the environment. The person seeking EPA approval must submit all information known to or reasonably ascertainable by the submitter on the microorganism( s) and the research and development activity, including information not May 10, 2004 listed in paragraphs ( c), ( d), and ( e) of this section that the person believes will be useful for EPA's risk assessment. The TERA must be in writing and must include at least the information described in the following paragraphs.

( b) When specific information is not submitted, an explanation of why such information is not available or not applicable must be included.

( c) Persons applying for a TERA, must include the submitter identification and microorganism identity information required for MCANs in § 725.155( c), ( d)( 1), and ( d)( 2).

( d) Persons applying for a TERA must submit phenotypic and ecological characteristics information required in § 725.155( d)( 3) as it relates directly to the conditions of the proposed research and development activity.

( e) Persons applying for a TERA must also submit the following information about the proposed research and development activity:

( 1) A detailed description of the proposed research and development activity. ( i) The objectives and significance of the activity and a rationale for testing the microorganisms in the environment. ( ii) Number of microorganisms released ( including viability per volume if applicable) and the method( s) of application or release. ( iii) Characteristics of the test site( s), including location, geographical, physical, chemical, and biological features, proximity to human habitation or activity, and description of site characteristics that would influence dispersal or confinement. ( iv) Target organisms ( if the microorganism( s) to be tested has an intended target), including identification of each target organism and anticipated mechanism and result of interaction. ( v) Planned start date and duration of each activity. ( vi) If State and/ or local authorities have been notified of the activity, evidence of notification.

( 2) Information on monitoring, confinement, mitigation, and emergency termination procedures. ( i) Confinement procedures for the activity, access and security measures, and procedures for routine termination of the activity. ( ii) Mitigation and emergency procedures. ( iii) Measures to detect and control potential adverse effects. ( iv) Name of principal investigator and chief of site personnel responsible for emergency procedures. ( v) Personal protective equipment, engineering controls, and procedures to be followed to minimize dispersion of the microorganism( s) by people, machinery, or equipment. ( vi) Procedures for disposal of any articles, waste, clothing, machinery, or other equipment involved in the experimental release, including methods for inactivation of the microorganism( s), containment, disinfection, and disposal of contaminated items.

§ 725.260 Submission of health and environmental effects data.

Each TERA must contain all available data concerning actual or potential effects on health or the environment of the new microorganism that are in the possession or control of the submitter and a May 10, 2004 description of other data known to or reasonably ascertainable by the submitter that will permit a reasoned evaluation of the planned test in the environment. The data must be reported in the manner described in § 725.160( a)( 3) and ( b)( 3).

§ 725.270 EPA review of the TERA.

General procedures for review of all submissions under this part are contained in § § 725.28 through 725.60. In addition, the following procedures apply to EPA review of applications submitted under this subpart:

( a) Length of the review period. ( 1) The review period for the TERA will be 60 days from the date the Document Control Officer for the Office of Pollution Prevention and Toxics receives a complete TERA, or the date EPA determines the TERA is complete under § 725.33, unless EPA finds good cause for an extension under § 725.56.

( 2) A submitter shall not proceed with the research and development activity described in the TERA unless and until EPA provides written approval of the TERA. A submitter may receive early approval if a review is completed in less than 60 days.

( b) EPA decision regarding proposed TERA activity. ( 1) A decision concerning a TERA under this subpart will be made by the Administrator, or a designee.

( 2) If EPA determines that the proposed research and development activity for the microorganism does not present an unreasonable risk of injury to health or the environment, EPA will notify the submitter that the TERA is approved and that the submitter can proceed with the proposed research and development activity described in the TERA.

( 3) EPA may include requirements and conditions in its approval of the TERA that would be stated in the TERA approval under paragraph ( c) of this section.

( 4) If EPA concludes that it cannot determine that the proposed research and development activity described in the TERA will not present an unreasonable risk of injury to health or the environment, EPA will deny the TERA and will provide reasons for the denial in writing.

( c) TERA approval. ( 1) A TERA approval issued by EPA under this section is legally binding on the TERA submitter.

( 2) When EPA approves a TERA, the submitter must conduct the research and development activity only as described in the TERA and in accordance with any requirements and conditions prescribed by EPA in its approval of the TERA.

( 3) Any person who fails to conduct the research and development activity as described in the TERA and in accordance with any requirements and conditions prescribed by EPA in its approval of the TERA under this section, shall be in violation of sections 5 and 15 of the Act and be subject to civil and criminal penalties under section 16 of the Act. May 10, 2004 § 725.288 Revocation or modification of TERA approval.

( a) Significant questions about risk. ( 1) If, after approval of a TERA under this subpart, EPA receives information which raises significant questions about EPA's determination that the activity does not present an unreasonable risk of injury to health or the environment, EPA will notify the submitter in writing of those questions.

( 2) The submitter may, within 10 days of receipt of EPA's notice, provide in writing additional information or arguments concerning the significance of the questions and whether EPA should modify or revoke the approval of the TERA.

( 3) After considering any such information and arguments, EPA will decide whether to change its determination regarding approval of the TERA. ( i) If EPA determines that the activity will not present an unreasonable risk of injury to health or the environment, it will notify the submitter in writing. To make this finding, EPA may prescribe additional conditions which must be followed by the submitter. ( ii) If EPA determines that it can no longer conclude that the activity will not present an unreasonable risk of injury to health or the environment, it will notify the submitter in writing that EPA is revoking its approval and state its reasons. In that event, the submitter must terminate the research and development activity within 48 hours of receipt of the notice in accordance with directions provided by EPA in the notice.

( b) Evidence of unreasonable risk. ( 1) If, after approval of a TERA under this subpart, EPA determines that the proposed research and development activity will present an unreasonable risk of injury to health or the environment, EPA will notify the submitter in writing and state its reasons.

( 2) In the notice, EPA may prescribe additional safeguards to address or reduce the risk, or may instruct the submitter to suspend the research and development activities.

( 3) Within 48 hours, the submitter must implement the instructions contained in the notice. The submitter may then submit additional information or arguments concerning the matters raised by EPA and whether EPA should modify or revoke the approval of the TERA in accordance with paragraph ( a)( 2) of this section.

( 4) EPA will consider the information and arguments in accordance with paragraph ( a)( 3) of this section.

( 5) Following consideration of the information and arguments under paragraph ( a)( 3) of this section, if EPA notifies the submitter that the R& D activity must be suspended or terminted, the submitter may resume the activity only upon written notice from EPA that EPA has approved resumption of the activity. In approving resumption of an activity, EPA may prescribe additional conditions which must be followed by the submitter.

( c) Modifications. If, after approval of a TERA under this subpart, the submitter concludes that it is necessary to alter the conduct of the research and development activity in a manner which would result in the activity being different from that described in the TERA agreement and any May 10, 2004 conditions EPA prescribed in its approval, the submitter must inform the EPA contact for the TERA and may not modify the activity without the approval of EPA.

Subpart F  Exemptions for Test Marketing § 725.300 Scope and purpose.

( a) This subpart describes exemptions from the reporting requirements under subpart D of this part for test marketing activities involving microorganisms.

( b) In lieu of complying with subpart D of this part, persons described in § 725.305 may submit an application for a test marketing exemption ( TME). ( c) Submission requirements specific for TME applications are described at § 725.350. ( d) Data requirements for TME applications are set forth in § 725.355. ( e) EPA review procedures specific for TMEs are set forth in § 725.370. ( f) Subparts A through C of this part apply to any submission under this subpart.

§ 725.305 Persons who may apply under this subpart.

A person identified in this section may apply for a test marketing exemption. EPA may grant the exemption if the person demonstrates that the microorganism will not present an unreasonable risk of injury to health or the environment as a result of the test marketing. A person may apply under this subpart for the following test marketing activities:

( a) A person who intends to manufacture or import for commercial purposes a new microorganism.

( b) A person who intends to manufacture, import, or process for commercial purposes a microorganism identified in subpart M of this part for a significant new use.

§ 725.350 Procedural requirements for this subpart.

General requirements for all submissions under this part are contained in subparts A through C of this part. In addition, the following requirements apply to applications submitted under this subpart:

( a) Prenotice consultation. EPA strongly suggests that for a TME, the applicant contact EPA for a prenotice consultation regarding eligibility for a TME.

( b) When to submit a TME application. Each person who is eligible to apply for a TME under this subpart must submit the application at least 45 calendar days before the person intends to commence the test marketing activity.

( c) Recordkeeping. Each person who is granted a TME must comply with the recordkeeping requirements of § 725.65. In addition, any person who obtains a TME must retain documentation of compliance with any restrictions imposed by EPA when it grants the TME. This information must be retained for 3 years from the final date of manufacture or import under the exemption. May 10, 2004 § 725.355 Information to be included in the TME application.

( a) To review a TME application, EPA must have sufficient information to permit a reasoned evaluation of the health and environmental effects of the planned test marketing activity. The person seeking EPA approval must submit all information known to or reasonably ascertainable by the person on the microorganism and the test marketing activity, including information not listed in paragraphs ( c), ( d), and ( e) of this section that the person believes will demonstrate that the microorganism will not present an unreasonable risk of injury to health or the environment as a result of the test marketing. The TME application must be in writing and must include at least the information described in paragraphs ( b), ( c), ( d), and ( e) of this section.

( b) When specific information is not submitted, an explanation of why such information is not available or not applicable must be included.

( c) Persons applying for a TME must submit the submitter identification and microorganism identity information required for MCANs in § 725.155( c), ( d)( 1), and ( d)( 2).

( d) Persons applying for a TME must submit phenotypic and ecological characteristics information required in § 725.155( d)( 3) as it relates directly to the conditions of the proposed test marketing activity.

( e) Persons applying for a TME must also submit the following information about the proposed test marketing activity:

( 1) Proposed test marketing activity. ( i) The maximum quantity of the microorganism which the applicant will manufacture or import for test marketing. ( ii) The maximum number of persons who may be provided the microorganism during test marketing. ( iii) The maximum number of persons who may be exposed to the microorganism as a result of test marketing, including information regarding duration and route of such exposures. ( iv) A description of the test marketing activity, including its duration and how it can be distinguished from full scale commercial production and research and development activities.

( 2) Health and environmental effects data. All existing data regarding health and environmental effects of the microorganism must be reported in accordance with § 725.160.

§ 725.370 EPA review of the TME application.

General procedures for review of all submissions under this part are contained in § § 725.28 through 725.60. In addition, the following procedures apply to EPA review of TME applications submitted under this subpart:

( a) No later than 45 days after EPA receives a TME, the Agency will either approve or deny the application. ( b) A submitter may only proceed with test marketing activities after receipt of EPA approval. ( c) In approving a TME application, EPA may impose any restrictions necessary to ensure that the microorganism will not present an unreasonable risk of injury to health and the environment as May 10, 2004 a result of test marketing.

Subpart G  General Exemptions for New Microorganisms § 725.400 Scope and purpose.

( a) This subpart describes exemptions from reporting under subpart D of this part, and from review under this part altogether, for manufacturing and importing of certain new microorganisms for commercial purposes. ( b) Recipient microorganisms eligible for the tiered exemption from review under this part are listed in § 725.420. ( c) Criteria for the introduced genetic material contained in the new microorganisms are described in § 725.421. ( d) Physical containment and control technologies are described in § 725.422. ( e) The conditions for the Tier I exemption are listed in § 725.424. ( f) In lieu of complying with subpart D of this part, persons using recipient microorganisms eligible for the tiered exemption may submit a Tier II exemption request. The limited reporting requirements for the Tier II exemption, including data requirements, are described in § § 725.450 and 725.455. ( g) EPA review procedures for the Tier II exemption are set forth in § 725.470. ( h) Subparts A through C of this part apply to any submission under this subpart.

§ 725.420 Recipient microorganisms.

The following recipient microorganisms are eligible for either exemption under this subpart:

( a) Acetobacter aceti. ( b) Aspergillus niger. ( c) Aspergillus oryzae. ( d) Bacillus licheniformis. ( e) Bacillus subtilis. ( f) Clostridium acetobutylicum. ( g) Escherichia coli K 12. ( h) Penicillium roqueforti. ( i) Saccharomyces cerevisiae. ( j) Saccharomyces uvarum.

§ 725.421 Introduced genetic material.

For a new microorganism to qualify for either exemption under this subpart, introduced genetic material must meet all of the criteria listed in this section.

( a) Limited in size. The introduced genetic material must consist only of the following:

( 1) The structural gene( s) of interest. ( 2) The regulatory sequences permitting the expression of solely the gene( s) of interest. ( 3) Associated nucleotide sequences needed to move genetic material, including linkers, May 10, 2004 homopolymers, adaptors, transposons, insertion sequences, and restriction enzyme sites. ( 4) The nucleotide sequences needed for vector transfer. ( 5) The nucleotide sequences needed for vector maintenance.

( b) Well characterized. For introduced genetic material, well characterized means that the following have been determined:

( 1) The function of all of the products expressed from the structural gene( s). ( 2) The function of sequences that participate in the regulation of expression of the structural gene( s). ( 3) The presence or absence of associated nucleotide sequences and their associated functions, where associated nucleotide sequences are those sequences needed to move genetic material including linkers, homopolymers, adaptors, transposons, insertion sequences, and restriction enzyme sites.

( c) Poorly mobilizable. The ability of the introduced genetic material to be transferred and mobilized is inactivated, with a resulting frequency of transfer of less than 10 8 transfer events per recipient.

( d) Free of certain sequences. ( 1) The introduced genetic material must not contain a functional portion of any of the toxin encoding sequences described in this paragraph ( d).

( i) For the purposes of this section, a functional portion of a toxin encoding sequence means any sequence which codes for a polypeptide that has one of the following effects: ( A) It directly or indirectly contributes to toxic effects in humans. Directly contributes to toxic effects in humans means those sequences encoding polypeptides that have direct toxicity to target cells. An example of a sequence which directly contributes to toxic effects in humans is one which encodes the portion of diphtheria toxin, listed in paragraph ( d)( 2) of this section, capable of interacting with elongation factor 2, leading to inhibition of protein synthesis in target respiratory, heart, kidney, and nerve tissues. Indirectly contributes to toxic effects in humans means a sequence whose encoded polypeptide is not directly toxic to target cells, yet still adversely affects humans. An example of a sequence which indirectly contributes to toxic effects is the sequence which encodes the portion of the botulinum toxin, listed in paragraph ( d)( 3) of this section, capable of blocking the release of acetylcholine from gangliosides. Botulinum toxin affects neuromuscular junctions by its blockage of acetylcholine release, leading to irreversible relaxation of muscles and respiratory arrest. ( B) It binds a toxin or toxin precursor to target human cells. ( C) It facilitates intracellular transport of a toxin in target human cells. ( ii) While these toxins are listed ( with synonyms in parentheses) in paragraphs ( d)( 2) through ( d)( 7) of this section according to the source organism, it is use of the nucleotide sequences that encode the toxins that is being restricted and not the use of the source organisms. The source organisms are listed to provide specificity in identification of sequences whose use is restricted. Although similar or identical sequences may be isolated from organisms other than hose listed below in paragraphs ( d)( 2) through ( d)( 7) of this section, these comparable toxin sequences, regardless of the organism from which they are derived, must not be included in the introduced genetic material. May 10, 2004 ( 2) Sequences for protein synthesis inhibitor.

Sequence Source Toxin Name Corynebacterium diphtheriae & C. Diphtheria toxin ulcerans Pseudomonas aeruginosa Exotoxin A Shigella dysenteriae Shigella toxin ( Shiga toxin, Shigella dysenteriae type I toxin, Vero cell toxin) Abrus precatorius, seeds Abrin Ricinus communis, seeds Ricin ( 3) Sequences for neurotoxins. Sequence Source Toxin Name Clostridium botulinum Neurotoxins A, B, C1, D, E, F, G ( Botulinum toxins, botulinal toxins) Clostridium tetani Tetanus toxin ( tetanospasmin) Proteus mirabilis Neurotoxin Staphylococcus aureus Alpha toxin ( alpha lysin) Yersinia pestis Murine toxin 1 1 Snake toxins ............................ Bungarus caeruleus Caeruleotoxin Bungarus multicinctus Beta bungarotoxin ( phospholipase) Crotalus spp. Crotoxin ( phospholipase) Dendroaspis viridis Neurotoxin Naja naja varieties Neurotoxin Notechia scutatus Notexin ( phospholipase) Oxyuranus scutellatus Taipoxin Invertebrate toxins Chironex fleckeri Neurotoxin Androctnus australis Neurotoxin Centruroides sculpturatus Neurotoxin ( 4) Sequences for oxygen labile cytolysins.

Sequence Source Toxin Name Bacillus alve Alveolysin Bacillus cereus Cereolysin May 10, 2004 Bacillus laterosporus Laterosporolysin Bacillus thuringiensis Thuringiolysin Clostridium bifermentans Lysin Clostridium botulinum Lysin Clostridium caproicum Lysin Clostridium chauvoei Delta toxin Clostridium histolyticum Epsilon toxin Clostridium novyi Gamma toxin Clostridium oedematiens Delta toxin Clostridium perfringens Theta toxin ( Perfringolysin) Clostridium septicum Delta toxin Clostridium sordellii Lysin Clostridium tetani Tetanolysin Listeria monocytogenes Listeriolysin ( A B) Streptococcus pneumoniae Pneumolysin Streptococcus pyogene Streptolysin O ( SLO)

( 5) Sequences for toxins affecting membrane function. Sequence Source Toxin Name Bacillus anthracis Edema factor ( Factors I II); Lethal factor ( Factors II III) Bacillus cereus Enterotoxin ( diarrheagenic toxin, mouse lethal factor) Bordetella pertussis Adenylate cyclase ( Heat labile factor); Pertussigen ( pertussis toxin, islet activating factor, histamine sensitizing factor, lymphocytosis promoting factor) Clostridium botulinum C2 toxin Clostridium difficile Enterotoxin ( toxin A) Clostridium perfringens Beta toxin; Delta toxin Escherichia coli & other Heat labile enterotoxins Enterobacteriaceae spp. ( LT); Heat stable enterotoxins ( STa, ST1 subtypes ST1a ST1b; also STb, STII) Legionella pneumophila Cytolysin Vibrio cholerae & Vibrio mimicus Cholera toxin ( choleragen)

( 6) Sequences that affect membrane integrity.

Sequence Source Toxin Name Clostridium bifermentans & other Lecithinase Clostridium spp Clostridium perfringens Alpha toxin ( phospholipase C, lecithinase); Enterotoxin Corynebacterium pyogenes & other Cytolysin ( phospholipase C), Corynebacterium spp. Ovis toxin ( sphingomyelinase D) Staphylococcus aureus Beta lysin ( beta toxin) May 10, 2004 ( 7) Sequences that are general cytotoxins.

Sequence Source Toxin Name Adenia digitata Modeccin Aeromonas hydrophila Aerolysin ( beta lysin, cytotoxic lysin) Clostridium difficile Cytotoxin ( toxin B) Clostridium perfringens Beta toxin; Epsilon toxin; Kappa toxin Escherichia coli & other Cytotoxin ( Shiga like toxin, Enterobacteriaceae spp. Vero cell toxin) Pseudomonas aeruginosa Proteases Staphylococcus aureus Gamma lysin ( Gamma toxin); Enterotoxins ( SEA, SEB, SEC, SED SEE); Pyrogenic exotoxins A B; Toxic shock syndrome toxins ( TSST 1) Staphylococcus aureus & Pseudomonas aeruginosa Leucocidin ( leukocidin, cytotoxin) Streptococcus pyogenes Streptolysin S ( SLS); Erythrogenic toxins( scarlet fever toxins, pyrogenic exotoxins) Yersinia enterocolitica Heat stable enterotoxins ( ST)

§ 725.422 Physical containment and control technologies.

The manufacturer must meet all of the following criteria for physical containment and control technologies for any facility in which the new microorganism will be used for a Tier I exemption; these criteria also serve as guidance for a Tier II exemption.

( a) Use a structure that is designed and operated to contain the new microorganism. ( b) Control access to the structure. ( c) Provide written, published, and implemented procedures for the safety of personnel and control of hygiene. ( d) Use inactivation procedures demonstrated and documented to be effective against the new microorganism contained in liquid and solid wastes prior to disposal of the wastes. The inactivation procedures must reduce viable microbial populations by at least 6 logs in liquid and solid wastes. ( e) Use features known to be effective in minimizing viable microbial populations in aerosols and exhaust gases released from the structure, and document use of such features. ( f) Use systems for controlling dissemination of the new microorganism through other routes, and document use of such features. ( g) Have in place emergency clean up procedures.

§ 725.424 Requirements for the Tier I exemption.

( a) Conditions of exemption. The manufacture or import of a new microorganism for commercial purposes is not subject to review under this part if all of the following conditions are met for all activities involving the new microorganism:

( 1) The recipient microorganism is listed in and meets any requirements specified in § 725.420. May 10, 2004 ( 2) The introduced genetic material meets the criteria under § 725.421. ( 3) The physical containment and control technologies of any facility in which the microorganism will be manufactured, processed, or used meet the criteria under § 725.422. ( 4) The manufacturer or importer submits a certification described in paragraph ( b) of this section to EPA at least 10 days before commencing initial manufacture or import of a new microorganism derived from a recipient microorganism listed in § 725.420. ( 5) The manufacturer or importer complies with the recordkeeping requirements of § 725.65 and maintains records for the initial and subsequent uses of the new microorganism that verify compliance with the following: ( i) The certifications made in paragraph ( b) of this section. ( ii) All the eligibility criteria for the Tier I exemption including the criteria for the recipient microorganism, the introduced genetic material, the physical containment and control technologies.

( b) Certification. To be eligible for the Tier I exemption under this subpart, the manufacturer or importer must submit to EPA a document signed by a responsible company official containing the information listed in this paragraph.

( 1) Name and address of manufacturer or importer. ( 2) Date when manufacture or import is expected to begin. ( 3) The identification ( genus, species) of the recipient microorganism listed in § 725.420 which is being used to create the new microorganism which will be used under the conditions of the Tier I exemption. ( 4) Certification of the following: ( i) Compliance with the introduced genetic material criteria described in § 725.421. ( ii) Compliance with the containment requirements described in § 725.422, including the provision in paragraph ( a)( 3) of this section. ( 5) The site of waste disposal and the type of permits for disposal, the permit numbers and the institutions issuing the permits. ( 6) The certification statement required in § 725.25( b). Certification of submission of test data is not required for the Tier I exemption.

§ 725.426 Applicability of the Tier I exemption.

The Tier I exemption under § 725.424 applies only to a manufacturer or importer of a new microorganism that certifies that the microorganism will be used in all cases in compliance with § § 725.420, 725.421, and 725.422.

§ 725.428 Requirements for the Tier II exemption.

The manufacturer or importer of a new microorganism for commercial purposes may submit to EPA a Tier II exemption request in lieu of a MCAN under subpart D of this part if all of the following conditions are met:

( a) The recipient microorganism is listed in and meets any requirements specified in § 725.420. ( b) The introduced genetic material meets the criteria under § 725.421. ( c) Adequate physical containment and control technologies are used. The criteria listed under May 10, 2004 § 725.422 for physical containment and control technologies of facilities should be used as guidance to satisfy the Tier II exemption request data requirements listed at § 725.455( d). EPA will review proposed process and containment procedures as part of the submission for a Tier II exemption under this section.

§ 725.450 Procedural requirements for the Tier II exemption.

General requirements for all submissions under this part are contained in § 725.25. In addition, the following requirements apply to requests submitted under this subpart:

( a) Prenotice consultation. EPA strongly suggests that for a Tier II exemption, the submitter contact the Agency for a prenotice consultation regarding eligibility for the exemption.

( b) When to submit the Tier II exemption request. Each person who is eligible to submit a Tier II exemption request under this subpart must submit the request at least 45 calendar days before the person intends to commence manufacture or import.

( c) Contents of the Tier II exemption request. Each person who submits a request under this subpart must provide the information described in § § 725.428 and 725.455, as well as information known to or reasonably ascertainable by the person that would permit EPA to determine that use of the microorganism, under the conditions specified in the request, will not present an unreasonable risk of injury to health or the environment.

( d) Recordkeeping. Each person who submits a request under this subpart must comply with the recordkeeping requirements of § 725.65. In addition, the submitter should maintain records which contain information that verifies compliance with the following:

( 1) The certifications made in the request. ( 2) All the eligibility criteria for the Tier II exemption request including the criteria for the recipient microorganism, the introduced genetic material, the physical containment and control technologies.

§ 725.455 Information to be included in the Tier II exemption request.

The submitter must indicate clearly that the submission is a Tier II exemption request for a microorganism instead of the MCAN under subpart D of this part and must submit the following information:

( a) Submitter identification. ( 1) The name and headquarters address of the submitter. ( 2) The name, address, and office telephone number ( including area code) of the principal technical contact representing the submitter.

( b) Microorganism identity information. ( 1) Identification ( genus, species, and strain) of the recipient microorganism. Genus, species designation should be substantiated by a letter from a culture collection or a brief summary of the results of tests conducted for taxonomic May 10, 2004 identification. ( 2) Type of genetic modification and the function of the introduced genetic material. ( 3) Site of insertion. ( 4) Certification of compliance with the introduced genetic material criteria described in § 725.421.

( c) Production volume. Production volume, including total liters per year, and the maximum cell concentration achieved during the production process.

( d) Process and containment information. ( 1) A description of the process including the following: ( i) Identity and location of the manufacturing site( s). ( ii) Process flow diagram illustrating the production process, including downstream separations, and indicating the containment envelope around the appropriate equipment. ( iii) Identities and quantities of feedstocks. ( iv) Sources and quantities of potential releases to both the workplace and environment, and a description of engineering controls, inactivation procedures, and other measures which will reduce worker exposure and environmental releases. ( v) A description of procedures which will be undertaken to prevent fugitive emissions, i. e. leak detection and repair program. ( vi) A description of procedures/ safeguards to prevent and mitigate accidental releases to the workplace and the environment. ( 2) Certification of those elements of the containment criteria described in § 725.422 with which the manufacturer is in compliance, including stating by number the elements with which the manufacturer is in full compliance.

( e) The site of waste disposal and the type of permits for disposal, the permit numbers and the institutions issuing the permits.

( f) The certification statement required in § 725.25( b). Certification of submission of test data is not required for the Tier II exemption.

§ 725.470 EPA review of the Tier II exemption request.

General procedures for review of all submissions under this part are contained in § § 725.28 through 725.60. In addition, the following procedures apply to EPA review of Tier II exemption requests submitted under this subpart:

( a) Length of the review period. The review period for the request will be 45 days from the date the Document Control Officer for the Office of Pollution Prevention and Toxics receives a complete request, or the date EPA determines the request is complete under § 725.33, unless the Agency extends the review period for good cause under § 725.56.

( b) Criteria for review. EPA will review the request to determine that the new microorganism complies with § 725.428 and that its manufacture, processing, use, and disposal as described in the request will not present an unreasonable risk of injury to health or the environment.

( c) EPA decision regarding the Tier II exemption request. A decision concerning a request under May 10, 2004 this subpart will be made by the Administrator, or a designee.

( d) Determination that the microorganism is ineligible for a Tier II review. ( 1) EPA may determine that the manufacturer or importer is not eligible for Tier II review, because the microorganism does not meet the criteria under § 725.428 or the Administrator, or a designee, decides that there is insufficient information to determine that the conditions of manufacture, processing, use, or disposal of the microorganism as described in the request will not present an unreasonable risk to health or the environment.

( 2) If the Agency makes this determination, the Administrator, or a designee will notify the manufacturer or importer by telephone, followed by a letter, that the request has been denied. The letter will explain reasons for the denial.

( 3) If the request is denied, the manufacturer or importer may submit the information necessary to constitute a MCAN under subpart D of this part.

( e) Approval or denial of the Tier II exemption request. ( 1) No later than 45 days after EPA receives a request, the Agency will either approve or deny the request.

( 2) In approving a request, EPA may impose any restrictions necessary to ensure that the microorganism will not present an unreasonable risk of injury to health and the environment as a result of general commercial use.

( f) EPA may seek to enjoin the manufacture or import of a microorganism in violation of this subpart, or act to seize any microorganism manufactured or imported in violation of this section or take other actions under the authority of sections 7 or 17 of the Act.

( g) A manufacturer or importer may only proceed after receipt of EPA approval.

Subparts H K [ Reserved]

Subpart L  Additional Procedures for Reporting on Significant New Uses of Microorganisms § 725.900 Scope and purpose.

( a) This subpart describes additional provisions governing submission of MCANs for microorganisms subject to significant new use rules identified in subpart M of this part.

( b) Manufacturers, importers, and processors described in § 725.105( c) must submit a MCAN under subpart D of this part for significant new uses of microorganisms described in subpart M of this part, unless they are excluded under § § 725.910 or 725.912.

( c) Section 725.920 discusses exports and imports.

( d) Additional recordkeeping requirements specific to significant new uses of microorganisms are described in § 725.950. May 10, 2004 ( e) Section 725.975 describes how EPA will approve alternative means of complying with significant new use requirements designated in subpart M of this part.

( f) Expedited procedures for promulgating significant new use requirements under subpart M of this part for microorganisms subject to section 5( e) orders are discussed in § § 725.980 and 725.984.

( g) This subpart L contains provisions governing submission and review of notices for the microorganisms and significant new uses identified in subpart M of this part. The provisions of this subpart L apply to the microorganisms and significant new uses identified in subpart M of this part, except to the extent that they are specifically modified or supplanted by specific requirements in subpart M of this part. In the event of a conflict between the provisions of this subpart L and the provisions of subpart M of this part, the provisions of subpart M of this part shall govern.

( h) The provisions of subparts A through F of this part also apply to subparts L and M of this part. For purposes of subparts L and M of this part, wherever the words " microorganism" or " new microorganism" appear in subparts A through F of this part, it shall mean the microorganism subject to subparts L and M of this part. In the event of a conflict between the provisions of subparts A through F and the provisions of subparts L and M of this part, the provisions of subparts L and M of this part shall govern.

§ 725.910 Persons excluded from reporting significant new uses.

( a) A person who intends to manufacture, import, or process a microorganism identified in subpart M of this part and who intends to distribute it in commerce is not required to submit a MCAN under subpart D of this part, if that person can document one or more of the following as to each recipient of the microorganism from that person:

( 1) That the person has notified the recipient, in writing, of the specific section in subpart M of this part which identifies the microorganism and its designated significant new uses, or ( 2) That the recipient has knowledge of the specific section in subpart M of this part which identifies the microorganism and its designated significant new uses, or ( 3) That the recipient cannot undertake any significant new use described in the specific section in subpart M of this part.

( b) The manufacturer, importer, or processor described in paragraph ( a) of this section must submit a MCAN under subpart D of this part, if such person has knowledge at the time of commercial distribution of the microorganism identified in the specific section in subpart M of this part that a recipient intends to engage in a designated significant new use of that microorganism without submitting a MCAN under this part.

( c) A person who processes a microorganism identified in a specific section in subpart M of this part for a significant new use of that microorganism is not required to submit a MCAN if that person can document each of the following: May 10, 2004 ( 1) That the person does not know the specific microorganism identity of the microorganism being processed, and ( 2) That the person is processing the microorganism without knowledge that the microorganism is identified in subpart M of this part.

( d)( 1) If at any time after commencing distribution in commerce of a microorganism identified in a specific section in subpart M of this part, a person who manufactures, imports, or processes a microorganism described in subpart M of this part and distributes it in commerce has knowledge that a recipient of the microorganism is engaging in a significant new use of that microorganism designated in that section without submitting a MCAN under this part, the person is required to cease supplying the microorganism to that recipient and to submit a MCAN for that microorganism and significant new use, unless the person is able to document each of the following: ( i) That the person has notified the recipient and EPA enforcement authorities ( at the address in paragraph ( d)( 1)( iii) of this section), in writing within 15 working days of the time the person develops knowledge that the recipient is engaging in a significant new use, that the recipient is engaging in a significant new use without submitting a MCAN. ( ii) That, within 15 working days of notifying the recipient as described in paragraph ( d)( 1)( i) of this section, the person received from the recipient, in writing, a statement of assurance that the recipient is aware of the terms of the applicable section in subpart M of this part and will not engage in the significant new use. ( iii) That the person has promptly provided EPA enforcement authorities with a copy of the recipient's statement of assurance described in paragraph ( d)( 1)( ii) of this section. The copy must be sent to the Director, Office of Compliance ( 2221A), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.

( 2) If EPA notifies the manufacturer, importer, or processor that the recipient is engaging in a significant new use after providing the statement of assurance described in paragraph ( d)( 1)( ii) of this section and without submitting a MCAN under this part, the manufacturer, importer, or processor shall immediately cease distribution to that recipient until the manufacturer, importer, or processor or the recipient has submitted a MCAN under this part and the MCAN review period has ended.

( 3) If, after receiving a statement of assurance from a recipient under paragraph ( d)( 1)( ii) of this section, a manufacturer, importer, or processor has knowledge that the recipient is engaging in a significant new use without submitting a MCAN under this part, the manufacturer, importer, or processor must immediately cease distributing the microorganism to that recipient and notify EPA enforcement authorities at the address identified in paragraph ( d)( 1)( iii) of this section. The manufacturer, importer, or processor may not resume distribution to that recipient until any one of the following has occurred: ( i) The manufacturer, importer, or processor has submitted a MCAN under this part and the MCAN review period has ended. ( ii) The recipient has submitted a MCAN under this part and the MCAN review period has ended. ( iii) The manufacturer, importer, or processor has received notice from EPA enforcement authorities that it may resume distribution to that recipient.

§ 725.912 Exemptions. May 10, 2004 Persons identified in § 725.105( c) are not required to submit a MCAN under subpart D of this part for a microorganism identified in subpart M of this part, unless otherwise specified in a specific section in subpart M, if:

( a) The person submits a MCAN for the microorganism prior to the promulgation date of the section in subpart M of this part which identifies the microorganism, and the person receives written notification of compliance from EPA prior to the effective date of such section. The MCAN submitter must comply with any applicable requirement of section 5( b) of the Act. The MCAN must include the information and test data specified in section 5( d)( 1) of the Act. For purposes of this exemption, the specific section in subpart M of this part which identifies the microorganism and § § 725.3, 725.15, 725.65, 725.70, 725.75, 725.100, and 725.900 apply; after the effective date of the section in subpart M of this part which identifies the microorganism, § § 725.105 and 725.910 apply and § 725.920 continues to apply. EPA will provide the MCAN submitter with written notification of compliance only if one of the following occurs:

( 1) EPA is unable to make the finding that the activities described in the MCAN will or may present an unreasonable risk of injury to health or the environment under reasonably foreseeable circumstances, or ( 2) EPA and the person negotiate a consent order under section 5( e) of the Act, such order to take effect on the effective date of the section in subpart M of this part which identifies the microorganism.

( b) The person is operating under the terms of a consent order issued under section 5( e) of the Act applicable to that person. If a provision of such section 5( e) order is inconsistent with a specific significant new use identified in subpart M of this part, abiding by the provision of the section 5( e) order exempts the person from submitting a MCAN for that specific significant new use.

§ 725.920 Exports and imports.

( a) Exports. Persons who intend to export a microorganism identified in subpart M of this part, or in any proposed rule which would amend subpart M of this part, are subject to the export notification provisions of section 12( b) of the Act. The regulations that interpret section 12( b) appear at part 707 of this chapter.

( b) Imports. Persons who import a substance identified in a specific section in subpart M of this part are subject to the import certification requirements under section 13 of the Act, which are codified at 19 CFR § § 12.118 through 12.127 and 127.28( i). The EPA policy in support of the import certification requirements appears at part 707 of this chapter.

§ 725.950 Additional recordkeeping requirements.

Persons submitting a MCAN for a significant new use of a microorganism must comply with the recordkeeping requirements of § 725.65. In addition, the following requirements apply: May 10, 2004 ( a) At the time EPA adds a microorganism to subpart M of this part, EPA may specify appropriate recordkeeping requirements. Each manufacturer, importer, and processor of the microorganism shall maintain the records for 3 years from the date of their creation.

( b) The records required to be maintained under this section may include the following:

( 1) Records documenting the information contained in the MCAN submitted to EPA.

( 2) Records documenting the manufacture and importation volume of the microorganism and the corresponding dates of manufacture and import.

( 3) Records documenting volumes of the microorganism purchased domestically by processors of the microorganism, names and addresses of suppliers and corresponding dates of purchase.

( 4) Records documenting the names and addresses ( including shipment destination address, if different) of all persons outside the site of manufacture or import to whom the manufacturer, importer, or processor directly sells or transfers the microorganism, the date of each sale or transfer, and the quantity of the microorganism sold or transferred on such date.

§ 725.975 EPA approval of alternative control measures.

( a) In certain sections of subpart M of this part, significant new uses for the identified microorganisms are described as the failure to establish and implement programs providing for the use of either: specific measures to control worker exposure to or release of microorganisms which are identified in such sections, or alternative measures to control worker exposure or environmental release which EPA has determined provide substantially the same degree of protection as the specified control measures. Persons who manufacture, import, or process a microorganism identified in such sections and who intend to employ alternative measures to control worker exposure or environmental release must submit a request to EPA for a determination of equivalency before commencing manufacture, import, or processing involving the alternative control measures.

( b) A request for a determination of equivalency must be submitted in writing to the Office of Pollution Prevention and Toxics, Document Control Officer, 7407, 1200 Pennsylvania Ave., NW., Washington, DC 20460: ATTN: SNUR Equivalency Determination, and must contain:

( 1) The name of the submitter. ( 2) The specific identity of the microorganism. ( 3) The citation for the specific section in subpart M of this part which pertains to the microorganism for which the request is being submitted. ( 4) A detailed description of the activities involved. ( 5) The specifications of the alternative worker exposure control measures or environmental release control measures. ( 6) A detailed analysis explaining why such alternative control measures provide substantially the same degree of protection as the specific control measures identified in the specific section in subpart M of this part which pertains to the microorganism for which the request is being May 10, 2004 submitted. ( 7) The data and information described in § § 725.155 and 725.160. If such data and information have already been submitted to EPA's Office of Pollution Prevention and Toxics, the submitter need only document that it was previously submitted, to whom, and the date it was submitted.

( c) Requests for determinations of equivalency will be reviewed by EPA within 45 days. Determinations under this paragraph will be made by the Director, or a designee. Notice of the results of such determinations will be mailed to the submitter.

( d) If EPA notifies the submitter under paragraph ( c) of this section that EPA has determined that the alternative control measures provide substantially the same degree of protection as the specified control measures identified in the specific section of subpart M of this part which pertains to the microorganism for which the request is being submitted, the submitter may commence manufacture, import, or processing in accordance with the specifications for alternative worker exposure control measures or environmental release control measures identified in the submitter's request, and may alter any corresponding notification to workers to reflect such alternative controls. Deviations from the activities described in the EPA notification constitute a significant new use and are subject to the requirements of this part.

§ 725.980 Expedited procedures for issuing significant new use rules for microorganisms subject to section 5( e) orders.

( a) Selection of microorganisms. ( 1) In accordance with the expedited process specified in this section, EPA will issue significant new use notification requirements for each new microorganism that, after MCAN review under subpart D of this part, becomes subject to a final order issued under section 5( e) of the Act, except for an order that prohibits manufacture and import of the microorganism, unless EPA determines that significant new use notification requirements are not needed for the microorganism.

( 2) If EPA determines that significant new use notifications requirements are not needed for a microorganism that is subject to a final order issued under section 5( e) of the Act, EPA will issue a notice in the FEDERAL REGISTER explaining why the significant new use requirements are not needed.

( b) Designation of requirements. ( 1) The significant new use notification and other specific requirements will be based on and be consistent with the provisions included in the final order issued for the microorganism under section 5( e) of the Act. EPA may also designate additional activities as significant new uses which will be subject to notification. ( 2) Significant new use requirements and other specific requirements designated under this section will be listed in subpart M of this part. For each microorganism, subpart M of this part will identify: ( i) The microorganism name. ( ii) The activities designated as significant new uses. ( iii) Other specific requirements applicable to the microorganism, including recordkeeping requirements or any other requirements included in the final section 5( e) order.

( c) Procedures for issuing significant new use rules. ( 1) Possible processes. EPA will issue May 10, 2004 significant new use rules ( SNURs) under this section by one of the following three processes: direct final rulemaking, interim final rulemaking, or notice and comment rulemaking. EPA will use the direct final rulemaking process to issue significant new use rules unless it determines that, in a particular case, one of the other processes is more appropriate. ( 2) Notice in the FEDERAL REGISTER. FEDERAL REGISTER documents issued to propose or establish significant new uses under this section will contain the following: ( i) The microorganism identity or, if its specific identity is claimed confidential, an appropriate generic microorganism name and an accession number assigned by EPA. ( ii) The MCAN number. ( iii) A summary of EPA's findings under section 5( e)( 1)( A) of the Act for the final order issued under section 5( e). ( iv) Designation of the significant new uses subject to, or proposed to be subject to, notification and any other applicable requirements. ( v) Any modification of subpart L of this part applicable to the specific microorganism and significant new uses. ( vi) If the FEDERAL REGISTER document establishes a final rule, or notifies the public that a final rule will not be issued after public comment has been received, the document will describe comments received and EPA's response. ( 3) Direct final rulemaking. ( i) EPA will use direct final rulemaking to issue a significant new use rule, when specific requirements will be based on and be consistent with the provisions included in the final order issued for the microorganism under section 5( e) of the Act. EPA will issue a final rule in the FEDERAL REGISTER following its decision to develop a significant new use rule under this section for a specific new microorganism. ( ii) The FEDERAL REGISTER document will state that, unless written notice is received by EPA within 30 days of publication that someone wishes to submit adverse or critical comments, the rule will be effective 60 days from the date of publication. The written notice of intent to submit adverse or critical comments should state which SNUR( s) will be the subject of the adverse or critical comments, if several SNURs are established through the direct final rule. If notice is received within 30 days that someone wishes to submit adverse or critical comments, the section( s) of the direct final rule containing the SNUR( s) for which a notice of intent to comment was received will be withdrawn by EPA issuing a document in the final rule section of the FEDERAL REGISTER, and a proposal will be published in the proposed rule section of the FEDERAL REGISTER. The proposal will establish a 30 day comment period.

( iii) If EPA, having considered any timely comments submitted in response to the proposal, decides to establish notification requirements under this section, EPA will issue a final rule adding the microorganism to subpart M of this part and designating the significant new uses subject to notification.

( 4) Interim final rulemaking. ( i) EPA will use the interim final rulemaking procedure to issue a significant new use rule, when specific requirements will be based on and be consistent with the provisions included in the final order issued for the microorganism under section 5( e) of the Act. The Agency will issue an interim final rule in the FEDERAL REGISTER following its decision to develop a significant new use rule for a specific new microorganism. The document will state EPA's reasons for using the interim final rulemaking procedure. ( A) The significant new use rule will take effect on the date of publication. ( B) Persons will be given 30 days from the date of publication to submit comments. May 10, 2004 ( ii) Interim final rules issued under this section shall cease to be in effect 180 days after publication unless, within the 180 day period, EPA issues a final rule in the FEDERAL REGISTER responding to any written comments received during the 30 day comment period specified in paragraph ( c)( 4)( i)( B) of this section and promulgating final significant new use notification requirements and other requirements for the microorganism.

( 5) Notice and comment rulemaking. ( i) EPA will use a notice and comment procedure to issue a significant new use rule, when EPA is designating additional activities which are not provisions included in the final order issued for the microorganism under section 5( e) of the Act as significant new uses which will be subject to notification. EPA will issue a proposal in the FEDERAL REGISTER following its decision to develop a significant new use rule under this section for a specific new microorganism. Persons will be given 30 days to comment on whether EPA should establish notification requirements for the microorganism under this part. ( ii) If EPA, having considered any timely comments, decides to establish notification requirements under this section, EPA will issue a final rule adding the microorganism to subpart M of this part and designating the significant new uses subject to notification.

( d) Schedule for issuing significant new use rules. ( 1) Unless EPA determines that a significant new use rule should not be issued under this section, EPA will issue a proposed rule, a direct final rule, or an interim final rule within180 days of receipt of a valid notice of commencement under § 725.190.

( 2) If EPA receives adverse or critical significant comments following publication of a proposed or interim final rule, EPA will either withdraw the rule or issue a final rule addressing the comments received.

§ 725.984 Modification or revocation of certain notification requirements.

( a) Criteria for modification or revocation. EPA may at any time modify or revoke significant new use notification requirements for a microorganism which has been added to subpart M of this part using the procedures of § 725.980. Such action may be taken under this section if EPA makes one of the following determinations, unless other information shows that the requirements should be retained:

( 1) Test data or other information obtained by EPA provide a reasonable basis for concluding that activities designated as significant new uses of the microorganism will not present an unreasonable risk of injury to health or the environment.

( 2) EPA has promulgated a rule under section 4 or 6 of the Act, or EPA or another agency has taken action under another law, for the microorganism that eliminates the need for significant new use notification under section 5( a)( 2) of the Act.

( 3) EPA has received MCANs for some or all of the activities designated as significant new uses of the microorganism and, after reviewing such MCANs, concluded that there is no need to require additional notice from persons who propose to engage in identical or similar activities.

( 4) EPA has examined new information, or has reexamined the test data or other information May 10, 2004 supporting its finding under section 5( e)( 1)( A)( ii)( I) of the Act and has concluded that a rational basis no longer exists for the findings that activities involving the microorganism may present an unreasonable risk of injury to health or the environment required under section 5( e)( 1)( A) of the Act.

( 5) Certain activities involving the microorganism have been designated as significant new uses pending the completion of testing, and adequate test data developed in accordance with applicable procedures and criteria have been submitted to EPA.

( b) Procedures for limitation or revocation. Modification or revocation of significant new use notification requirements for a microorganism that has been added to subpart M of this part using the procedures described in § 725.980 may occur either at EPA's initiative or in response to a written request.

( 1) Any affected person may request modification or revocation of significant new use notification requirements for a microorganism that has been added to subpart M of this part using the procedures described in § 725.980 by writing to the Director, or a designee, and stating the basis for such request. The request must be accompanied by information sufficient to support the request. All requests should be sent to the TSCA Document Processing Center ( 7407), Room L 100, U. S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460, ATTN: Request to amend SNUR.

( 2) The Director, or a designee, will consider the request, make a determination whether to initiate rulemaking to modify the requirements, and notify the requester of that determination by certified letter. If the request is denied, the letter will explain why EPA has concluded that the significant new use notification requirements for that microorganism should remain in effect.

( 3) If EPA concludes that significant new use notification requirements for a microorganism should be limited or revoked, EPA will propose the changes in a notice in the FEDERAL REGISTER, briefly describe the grounds for the action, and provide interested parties an opportunity to comment.

Subpart M  Significant New Uses for Specific Microorganisms § 725.1000 Scope.

This subpart identifies uses of microorganisms which EPA has determined to be significant new uses under the authority of section 5( a)( 2) of the Toxic Substances Control Act.

§ 725.1075 Burkholderia cepacia complex.

( a) Microorganism and significant new uses subject to reporting. ( 1) The microorganisms identified as the Burkholderia cepacia complex defined as containing the following nine species, Burkholderia cepacia, Burkholderia multivorans, Burkholderia stabilis, Burkholderia vietnamiensis, Burkholderia ambifaria, Burkholderia pyrrocinia, Burkholderia cepacia genomovar VIII ( Burkholderia anthina), and Burkholderia cepacia genomovars III and VI are subject to reporting under this section for the significant new uses described in paragraph ( a)( 2) of this May 10, 2004 section.

( 2) The significant new use is any use other than research and development in the degradation of chemicals via injection into subsurface groundwater.

( b) [ Reserved]

[ 68 FR 35320, June 13, 2003] May 10, 2004 Attachment G Premanufacture Notice ( EPA Form 7710 25) May 10, 2004 Attachment H Instruction Manual for Reporting under the TSCA Section 5 New Chemicals Program