(a) This part establishes all reporting requirements under section 5 of TSCA for manufacturers, importers, and processors of microorganisms subject to TSCA jurisdiction for commercial purposes, including research and development for commercial purposes. New microorganisms for which manufacturers and importers are required to report under section 5(a)(1)(A) of TSCA are those that are intergeneric. In addition, under section 5(a)(1)(B) of TSCA, manufacturers, importers, and processors may be required to report for any microorganism that EPA determines by rule is being manufactured, imported, or processed for a significant new use.

(b) Any manufacturer, importer, or processor required to report under section 5 of TSCA (see § 725.100 for new microorganisms and § 725.900 for significant new uses) must file a Microbial Commercial Activity Notice (MCAN) with EPA, unless the activity is eligible for a specific exemption as described in this part. The general procedures for filing MCANs are described in subpart D of this part. The exemptions from the requirement to file a MCAN are for certain kinds of contained activities (see §§ 725.424 and 725.428), test marketing activities (see § 725.300), and research and development activities described in paragraph (c) of this section.

(c) Any manufacturer, importer, or processor required to file a MCAN for research and development (R&D) activities may instead file a TSCA Experimental Release Application (TERA) for a specific test (see § 725.250). A TERA is not required for certain R&D activities; however a TERA exemption does not extend beyond the research and development stage, to general commercial use of the microorganism, for which compliance with MCAN requirements is required. The TERA exemptions are for R&D activities subject to other Federal agencies or programs (see § 725.232), certain kinds of contained R&D activities (see § 725.234), and R&D activities using certain listed microorganisms (see § 725.238).

(d) New microorganisms will be added to the Inventory established under section 8 of TSCA once a MCAN has been received, the MCAN review period has expired, and EPA receives a Notice of Commencement (NOC) indicating that manufacture or importation has actually begun. New microorganisms approved for use under a TERA will not be added to the Inventory until a MCAN has been received, the MCAN review period has expired, and EPA has received an NOC.

Definitions in section 3 of the Act (15 U.S.C. 2602), as well as definitions contained in §§ 704.3, 720.3, and 721.3 of this chapter, apply to this part unless otherwise specified in this section. In addition, the following definitions apply to this part:

Consolidated microbial commercial activity notice or consolidated MCAN means any MCAN submitted to EPA that covers more than one microorganism (each being assigned a separate MCAN number by EPA) as a result of a prenotice agreement with EPA.

Containment and/or inactivation controls means any combination of engineering, mechanical, procedural, or biological controls designed and operated to restrict environmental release of viable microorganisms from a structure.

Director means the Director of the EPA Office of Pollution Prevention and Toxics.

Exemption request means any application submitted to EPA under subparts E, F, or G of this part.

General commercial use means use for commercial purposes other than research and development.

Genome means the sum total of chromosomal and extrachromosomal genetic material of an isolate and any descendants derived under pure culture conditions from that isolate.

Health and safety study of a microorganism or health and safety study means any study of any effect of a microorganism or microbial mixture on health or the environment or on both, including underlying data and epidemiological studies, studies of occupational exposure to a microorganism or microbial mixture, toxicological, clinical, and ecological, or other studies of a microorganism or microbial mixture, and any test performed under the Act. Microorganism identity is always part of a health and safety study of a microorganism.

(1) It is intended that the term “health and safety study of a microorganism” be interpreted broadly. Not only is information which arises as a result of a formal, disciplined study included, but other information relating to the effects of a microorganism or microbial mixture on health or the environment is also included. Any data that bear on the effects of a microorganism on health or the environment would be included.

(2) Examples include:

(i) Tests for ecological or other environmental effects on invertebrates, fish, or other animals, and plants, including: Acute toxicity tests, chronic toxicity tests, critical life stage tests, behavioral tests, algal growth tests, seed germination tests, plant growth or damage tests, microbial function tests, bioconcentration or bioaccumulation tests, and model ecosystem (microcosm) studies.

(ii) Long- and short-term tests of mutagenicity, carcinogenicity, or teratogenicity; dermatoxicity; cumulative, additive, and synergistic effects; and acute, subchronic, and chronic effects.

(iii) Assessments of human and environmental exposure, including workplace exposure, and impacts of a particular microorganism or microbial mixture on the environment, including surveys, tests, and studies of: Survival and transport in air, water, and soil; ability to exchange genetic material with other microorganisms, ability to colonize human or animal guts, and ability to colonize plants.

(iv) Monitoring data, when they have been aggregated and analyzed to measure the exposure of humans or the environment to a microorganism.

(v) Any assessments of risk to health and the environment resulting from the manufacture, processing, distribution in commerce, use, or disposal of the microorganism.

Inactivation means that living microorganisms are rendered nonviable.

Institutional Biosafety Committee means the committees described in the NIH Guidelines in section IV.B.2.

Intergeneric microorganism means a microorganism that is formed by the deliberate combination of genetic material originally isolated from organisms of different taxonomic genera.

(1) The term “intergeneric microorganism” includes a microorganism which contains a mobile genetic element which was first identified in a microorganism in a genus different from the recipient microorganism.

(2) The term “intergeneric microorganism” does not include a microorganism which contains introduced genetic material consisting of only well-characterized, non-coding regulatory regions from another genus.

Introduced genetic material means genetic material that is added to, and remains as a component of, the genome of the recipient.

Manufacture, import, or process for commercial purposes means:

(1) To import, produce, manufacture, or process with the purpose of obtaining an immediate or eventual commercial advantage for the manufacturer, importer, or processor, and includes, among other things, “manufacture” or “processing” of any amount of a microorganism or microbial mixture:

(i) For commercial distribution, including for test marketing.

(ii) For use by the manufacturer, including use for product research and development or as an intermediate.

(2) The term also applies to substances that are produced coincidentally during the manufacture, processing, use, or disposal of another microorganism or microbial mixture, including byproducts that are separated from that other microorganism or microbial mixture and impurities that remain in that microorganism or microbial mixture. Byproducts and impurities without separate commercial value are nonetheless produced for the purpose of obtaining a commercial advantage, since they are part of the manufacture or processing of a microorganism for commercial purposes.

Microbial commercial activity notice or MCAN means a notice for microorganisms submitted to EPA pursuant to section 5(a)(1) of the Act in accordance with subpart D of this part.

Microbial mixture means any combination of microorganisms or microorganisms and other chemical substances, if the combination does not occur in nature and is not an article.

Microorganism means an organism classified, using the 5-kingdom classification system of Whittacker, in the kingdoms Monera (or Procaryotae), Protista, Fungi, and the Chlorophyta and the Rhodophyta of the Plantae, and a virus or virus-like particle.

Mobile genetic element or MGE means an element of genetic material that has the ability to move genetic material within and between organisms. “Mobile genetic elements” include all plasmids, viruses, transposons, insertion sequences, and other classes of elements with these general properties.

New microorganism means a microorganism not included on the Inventory.

NIH Guidelines means the National Institutes of Health (NIH) “Guidelines for Research Involving Recombinant DNA Molecules” (July 5, 1994).

Non-coding regulatory region means a segment of introduced genetic material for which:

(1) The regulatory region and any inserted flanking nucleotides do not code for protein, peptide, or functional ribonucleic acid molecules.

(2) The regulatory region solely controls the activity of other regions that code for protein or peptide molecules or act as recognition sites for the initiation of nucleic acid or protein synthesis.

Small quantities solely for research and development (or “small quantities solely for purposes of scientific experimentation or analysis or research on, or analysis of, such substance or another substance, including such research or analysis for development of a product”) means quantities of a microorganism manufactured, imported, or processed or proposed to be manufactured, imported, or processed solely for research and development that meet the requirements of § 725.234.

Structure means a building or vessel which effectively surrounds and encloses the microorganism and includes features designed to restrict the microorganism from leaving.

Submerged standard industrial fermentation means a fermentation system that meets all of the following conditions:

(1) Enzyme production is conducted under conditions of submerged fermentation (i.e., growth of the microorganism occurs beneath the surface of the liquid growth medium).

(2) Any fermentation of solid plant material or insoluble substrates, to which T. reesei fermentation broth is added after the submerged standard industrial fermentation operations used for enzyme production is completed, may be initiated only after the inactivation of the microorganism as delineated in 40 CFR 725.422(d).

Submission means any MCAN or exemption request submitted to EPA under this part.

Technically qualified individual means a person or persons:

(1) Who, because of education, training, or experience, or a combination of these factors, is capable of understanding the health and environmental risks associated with the microorganism which is used under his or her supervision,

(2) Who is responsible for enforcing appropriate methods of conducting scientific experimentation, analysis, or microbiological research to minimize such risks, and

(3) Who is responsible for the safety assessments and clearances related to the procurement, storage, use, and disposal of the microorganism as may be appropriate or required within the scope of conducting a research and development activity.

TSCA Experimental Release Application or TERA means an exemption request for a research and development activity, which is not eligible for a full exemption from reporting under § 725.232, 725.234, or 725.238, submitted to EPA in accordance with subpart E of this part.

Well-characterized for introduced genetic material 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.

(a) Microorganisms subject to this part. Only microorganisms which are manufactured, imported, or processed for commercial purposes, as defined in § 725.3, are subject to the requirements of this part.

(b) Microorganisms automatically included on the Inventory. Microorganisms that are not intergeneric are automatically included on the Inventory.

(c) Microorganisms not subject to this part. The following microorganisms are not subject to this part, either because they are not subject to jurisdiction under the Act or are not subject to reporting under section 5 of the Act.

(1) Any microorganism which would be excluded from the definition of “chemical substance” in section 3 of the Act and § 720.3(e) of this chapter.

(2) Any microbial mixture as defined in § 725.3. This exclusion applies only to a microbial mixture as a whole and not to any microorganisms and other chemical substances which are part of the microbial mixture.

(3) Any microorganism that is manufactured and processed solely for export if the following conditions are met:

(i) The microorganism is labeled in accordance with section 12(a)(1)(B) of the Act, when the microorganism is distributed in commerce.

(ii) The manufacturer and processor can document at the commencement of manufacturing or processing that the person to whom the microorganism will be distributed intends to export it or process it solely for export as defined in § 721.3 of this chapter.

To identify and list microorganisms on the Inventory, both taxonomic designations and supplemental information will be used. The supplemental information required in paragraph (b) of this section will be used to specifically describe an individual microorganism on the Inventory. Submitters must provide the supplemental information required by paragraph (b) of this section to the extent necessary to enable a microorganism to be accurately and unambiguously identified on the Inventory.

(a) Taxonomic designation. The taxonomic designation of a microorganism must be provided for the donor organism and the recipient microorganism to the level of strain, as appropriate. These designations must be substantiated by a letter from a culture collection, literature references, or the results of tests conducted for the purpose of taxonomic classification. Upon EPA's request to the submitter, data supporting the taxonomic designation must be provided to EPA. The genetic history of the recipient microorganism should be documented back to the isolate from which it was derived.

(b) Supplemental information. The supplemental information described in paragraphs (b)(1) and (b)(2) of this section is required to the extent that it enables a microorganism to be accurately and unambiguously identified.

(1) Phenotypic information. Phenotypic information means pertinent traits that result from the interaction of a microorganism's genotype and the environment in which it is intended to be used and may include intentionally added biochemical and physiological traits.

(2) Genotypic information. Genotypic information means the pertinent and distinguishing genotypic characteristics of a microorganism, such as the identity of the introduced genetic material and the methods used to construct the reported microorganism. This also may include information on the vector construct, the cellular location, and the number of copies of the introduced genetic material.

(a) Consulting EPA. Persons intending to conduct activities involving microorganisms may determine their obligations under this part by consulting the Inventory or the microorganisms and uses specified in § 725.239 or in subpart M of this part. This section establishes procedures for EPA to assist persons in determining whether the microorganism or the use is listed on the Inventory, in § 725.239 or in subpart M of this part.

(1) Confidential identity or use. In some cases it may not be possible to directly determine if a specific microorganism is listed, because portions of that entry may contain generic information to protect confidential business information (CBI). If any portion of the microorganism's identity or use has been claimed as CBI, that portion does not appear on the public version of the Inventory, in § 725.239 or in subpart M of this part. Instead, it is contained in a confidential version held in EPA's Confidential Business Information Center (CBIC). The public versions contain generic information which masks the confidential business information. A person who intends to conduct an activity involving a microorganism or use whose entry is described with generic information will need to inquire of EPA whether the unreported microorganism or use is on the confidential version.

(2) Uncertain microorganism identity. The current state of scientific knowledge leads to some imprecision in describing a microorganism. As the state of knowledge increases, EPA will be developing policies to determine whether one microorganism is equivalent to another. Persons intending to conduct activities involving microorganisms may inquire of EPA whether the microorganisms they intend to manufacture (including import) or process are equivalent to specific microorganisms described on the Inventory, in § 725.239, or in subpart M of this part.

(b) Requirement of bona fide intent. (1) EPA will answer the inquiries described in paragraph (a) of this section only if the Agency determines that the person has a bona fide intent to conduct the activity for which reporting is required or for which any exemption may apply.

(2) To establish a bona fide intent to manufacture (including import) or process a microorganism, the person who proposes to manufacture (including import) or process the microorganism must submit the request to EPA via CDX. Prior to submission to EPA via CDX, such bona fide intents to manufacture (including import) or process must be generated and completed using e-PMN software. See 40 CFR 720.40(a)(2)(ii) for information on how to access the e-PMN software. A bona fide intent to manufacture (including import) or process must contain the following information:

(i) Taxonomic designations and supplemental information required by § 725.12.

(ii) A signed statement certifying that the submitter intends to manufacture (including import) or process the microorganism for commercial purposes.

(iii) A description of research and development activities conducted with the microorganism to date, demonstration of the submitter's ability to produce or obtain the microorganism from a foreign manufacturer, and the purpose for which the person will manufacture (including import) or process the microorganism.

(iv) An indication of whether a related microorganism was previously reviewed by EPA to the extent known by the submitter.

(v) A specific description of the major intended application or use of the microorganism.

(c) If an importer or processor cannot provide all the information required by paragraph (b) of this section, because it is claimed as confidential business information by its foreign manufacturer or supplier, the foreign manufacturer or supplier may supply the information directly to EPA.

(d) EPA will review the information submitted by the manufacturer (including importer) or processor under this paragraph to determine whether that person has shown a bona fide intent to manufacture (including import) or process the microorganism. If necessary, EPA will compare this information to the information requested for the confidential microorganism under § 725.85(b)(3)(iii).

(e) In order for EPA to make a conclusive determination of the microorganism's status, the proposed manufacturer (including importer) or processor must show a bona fide intent to manufacture (including import) or process the microorganism and must provide sufficient information to establish identity unambiguously. After sufficient information has been provided, EPA will inform the manufacturer (including importer) or processor whether the microorganism is subject to this part and if so, which sections of this part apply.

(f) If the microorganism is found on the confidential version of the Inventory, in § 725.239 or in subpart M of this part, EPA will notify the person(s) who originally reported the microorganism that another person (whose identity will remain confidential, if so requested) has demonstrated a bona fide intent to manufacture (including import) or process the microorganism and therefore was told that the microorganism is on the Inventory, in § 725.239, or in subpart M of this part.

(g) A disclosure to a person with a bona fide intent to manufacture (including import) or process a particular microorganism that the microorganism is on the Inventory, in § 725.239, or in subpart M of this part will not be considered a public disclosure of confidential business information under section 14 of the Act.

(h) EPA will answer an inquiry on whether a particular microorganism is subject to this part within 30 days after receipt of a complete submission under paragraph (b) of this section.

Persons may consult with EPA, either in writing or by telephone, about their obligations under this part. Written consultation is preferred. Written inquiries should be sent to the following address: Environmental Assistance Division (7408), Office of Pollution Prevention and Toxics, U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460, ATTN: Biotechnology Notice Consultation. Persons wishing to consult with EPA by telephone should call (202) 554-1404; hearing impaired TDD (202) 554-0551 or e-mail: [email protected].