[Federal Register Volume 62, Number 70 (Friday, April 11, 1997)]
[Rules and Regulations]
[Pages 17910-17958]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-8669]



[[Page 17909]]

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Part II





Environmental Protection Agency





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40 CFR Parts 700, 720, 721, 723, and 725



Microbial Products of Biotechnology; Final Regulation Under the Toxic 
Substances Control Act; Final Rule

  Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules 
and Regulations  

[[Page 17910]]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Parts 700, 720, 721, 723, and 725

[OPPTS-00049C; FRL-5577-2]
RIN 2070-AB61


Microbial Products of Biotechnology; Final Regulation Under the 
Toxic Substances Control Act

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: EPA is promulgating this final rule under section 5 of the 
Toxic Substances Control Act (TSCA), 15 U.S.C 2604, to establish 
notification procedures for review of certain new microorganisms before 
they are introduced into commerce. ``New'' microorganisms are those 
formed by deliberate combinations of genetic material from organisms 
classified in different taxonomic genera. This review process is 
designed to prevent unreasonable risk of injury to human health and the 
environment without imposing unnecessary regulatory burdens on the 
biotechnology industry. This final rule describes notification 
procedures and the microorganisms that would be exempt from 
notification.

DATES: This rule will become effective June 10, 1997. In accordance 
with 40 CFR 23.5, this rule shall be promulgated for purposes of 
judicial review at 1 p.m. eastern daylight savings time on April 27, 
1997.

FOR FURTHER INFORMATION CONTACT: For general information including 
copies of this document and related materials: Susan Hazen, Director, 
Environmental Assistance Division (7408), Office of Pollution 
Prevention and Toxics, Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460, Telephone: (202-554-1404), TDD: (202-554-0551), 
e-mail address: TSCA-H[email protected].
    For technical information regarding this document: David 
Giamporcaro, Office of Pollution Prevention and Toxics (7405), 
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. 
Telephone: (202-260-6362).

SUPPLEMENTARY INFORMATION:
Electronic Availability: Electronic copies of this document and various 
support documents are available from the EPA home page at the 
Environmental Sub-Set entry for this document under ``Regulations'' 
(http://www.epa.gov/fedrgstr/). The final rule may also be accessed at 
the Office of Pollution Prevention and Toxics Biotechnology home page 
at http://www.epa.gov/opptintr/biotech/. Fax-On-Demand: Using a 
faxphone call 202-401-0527 and select item 3100 for an index of 
available material and corresponding item numbers related to this 
document.
    This rule establishes procedures for the premanufacture review of 
certain new microbial products of biotechnology that are comparable to 
those for traditional chemical substances but are tailored to address 
the specific characteristics of these microorganisms. EPA published its 
final TSCA section 5 premanufacture notification (PMN) rule (40 CFR 
part 720) on May 13, 1983 (48 FR 21722) and subsequently amended 
certain parts of the rule on September 13, 1983 (48 FR 41132), April 
22, 1986 (51 FR 15096), and March 29, 1995 (60 FR 16298) (FRL-4921-8). 
In 1984, EPA discussed how the PMN rule could be applied to 
microorganisms in ``Proposed Policy Regarding Certain Microbial 
Products'' which was published as part of the Federal ``Proposal for a 
Coordinated Framework for Regulation of Biotechnology; Notice'' (``1984 
Proposed Policy Statement'') which was published by the Office of 
Science and Technology Policy (OSTP) on December 31, 1984 (49 FR 
50856). In 1986, EPA stated how the PMN rule would be applied to 
microorganisms in the ``Statement of Policy: Microbial Products Subject 
to the Federal Insecticide, Fungicide, and Rodenticide Act and Toxic 
Substances Control Act'' (``1986 Policy Statement''), which was 
published as part of the Federal ``Coordinated Framework for Regulation 
of Biotechnology; Announcement of Policy and Notice for Public 
Comment'' which was published by OSTP on June 26, 1986 (51 FR 23302). 
On September 1, 1994, EPA published the proposed rule, ``Microbial 
Products of Biotechnology; Proposed Regulation Under the Toxic 
Substances Control Act,'' which would, when finalized, fully implement 
its program for microorganisms under TSCA section 5 (59 FR 45526) (FRL-
4778-4). While general background information is presented here, 
readers should also consult the preambles of those documents for 
further information on the development of the biotechnology program 
under TSCA section 5.
Regulated Entities. Potentially regulated entities are persons 
conducting commercial research and development activities or persons 
manufacturing, importing, or processing for commercial purposes 
intergeneric microorganisms used for a TSCA purpose. Regulated 
categories and entities include:

                                                                        
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                                               Examples of Regulated    
                 Category                             Entities          
------------------------------------------------------------------------
Biotechnology research and development     Persons conducting commercial
 activities involving commercial funds      research using intergeneric 
                                            microorganisms for          
                                            biofertilizers; biosensors; 
                                            biotechnology reagents;     
                                            commodity or specialty      
                                            chemical production; energy 
                                            applications; waste         
                                            treatment or pollutant      
                                            degradation; and other TSCA 
                                            subject uses.               
------------------------------------------------------------------------
Commercial biotechnology products          Persons manufacturing,       
                                            importing or processing     
                                            products for commercial     
                                            purposes intergeneric       
                                            microorganisms for          
                                            biofertilizers; biosensors; 
                                            biotechnology reagents;     
                                            commodity or specialty      
                                            chemical production; energy 
                                            applications; waste         
                                            treatment or pollutant      
                                            degradation; and other TSCA 
                                            subject uses.               
------------------------------------------------------------------------

    This table is not intended to be exhaustive, but rather provides a 
guide for readers regarding entities likely to be regulated by this 
action. This table lists the types of entities that EPA is now aware 
could potentially be regulated by this action. Other types of entities 
not listed in the table could also be regulated. To determine whether 
your intergeneric microorganism is regulated by this action, you should 
carefully examine the list of substances excluded by TSCA section 
(3)(2)(B), and the requirements for ``persons who must report'' in 
Sec. 725.205 of the regulatory text for research and development 
activities using intergeneric microorganisms and Sec. 725.105 of the

[[Page 17911]]

regulatory text for manufacturing, importing, and processing 
intergeneric microorganisms. If you have questions regarding the 
applicability of this action to a particular entity, consult the person 
listed in the preceding FOR FURTHER INFORMATION CONTACT unit.

I. Background

A. Statutory Authority

    TSCA section 5(a)(1) requires that persons notify EPA at least 90 
days before they manufacture or import for commercial purposes a 
``new'' chemical substance or manufacture, import, or process a 
chemical substance for a ``significant new use.'' TSCA defines 
``chemical substance'' broadly and in terms which cover microorganisms 
as well as traditional chemicals. Therefore, for the purposes of TSCA, 
a ``new microorganism,'' like a ``new chemical substance,'' is one that 
is not listed on the TSCA Chemical Substances Inventory compiled under 
TSCA section 8(b). TSCA section 5(h)(3) exempts the manufacture or 
importation of small quantities of chemical substances produced solely 
for research and development (R&D) from the section 5 notification 
requirements if the manufacturer or importer notifies persons engaged 
in R&D of any health risks that the company or EPA has reason to 
believe may be associated with the chemical substance. TSCA section 
5(h)(3) authorizes EPA to define by rule what constitutes small 
quantities and to prescribe the form and manner of risk notification. 
TSCA section 5(h)(4) authorizes EPA, upon application and by rule, to 
exempt the manufacturer or importer of any new chemical substance from 
part or all of the provisions of section 5, if EPA determines that the 
manufacture, processing, distribution in commerce, use, or disposal of 
the new chemical substance will not present an unreasonable risk of 
injury to human health or the environment.

B. History

    This rule implements EPA's program for oversight of microorganisms, 
in accordance with the 1986 Policy Statement. Since its publication, 
EPA has been operating its biotechnology program under the 1986 Policy 
Statement. Prior to the 1986 Policy Statement, EPA issued the 1984 
Proposed Policy Statement. Subsequent to the 1986 Policy Statement, EPA 
issued a notice, entitled ``Biotechnology; Request for Comment on 
Regulatory Approach'' on February 15, 1989 (54 FR 7027), in order to 
solicit comments on the direction of EPA's biotechnology program under 
TSCA. Comments on the 1984 and 1986 documents and the February 15, 1989 
Federal Register notice are addressed, as appropriate, in this 
preamble.
    On September 7, 1990, EPA convened a subcommittee of its 
Biotechnology Science Advisory Committee (Subcommittee on 
Implementation of Scope) to comment on topics associated with the 
proposed rule. EPA again convened a subcommittee, the Subcommittee on 
the Proposed Biotechnology Rule under TSCA, which met on July 22, 1991. 
Advice from both of these subcommittees was incorporated as appropriate 
in the preamble to the proposed rules, and summaries of subcommittee 
deliberations were placed in the docket for this rulemaking. On 
September 1, 1994, EPA published the proposed rules ``Microbial 
Products of Biotechnology; Proposed Regulation Under the Toxic 
Substances Control Act'' (59 FR 45526). The final rule announced today 
is intended to describe implementation of EPA's program for regulation 
of microorganisms under TSCA.

II. Summary of Proposed Rule

    EPA proposed to establish a new part 725 of Title 40 of the Code of 
Federal Regulations (CFR). EPA believed that consolidating all 
requirements and procedures applicable to new microorganisms into one 
part of the CFR was appropriate and justified because of the specific 
characteristics of microorganisms. The consolidation was expected to 
benefit the public by providing greater focus and enhanced clarity. 
Part 725 is devoted exclusively to the review of microorganisms under 
section 5 of TSCA and is divided into eight subparts. Subparts A, B, 
and C consolidated provisions primarily adapted from parts 720 and 721. 
Subpart A, which includes definitions that are applicable throughout 
part 725, described general provisions and applicability. Subpart B 
described administrative procedures that are applicable to all 
submissions under part 725. Subpart C described confidentiality 
provisions that are applicable to all submissions under part 725.
    Subpart D, which combined the general PMN and significant new use 
notice (SNUN) requirements adapted from parts 720 and 721, described 
the reporting requirements and review process pertaining to microbial 
commercial activity notices (MCANs). Subparts E, F, and G described the 
reporting requirements and review processes for applications for 
exemptions from full MCAN reporting. Subpart E, which was almost 
entirely new, described a new reporting process using the TSCA 
experimental release application (TERA) which was developed for 
reporting research and development (R&D) activities involving release 
to the environment. Subpart E also described who would be eligible to 
submit a TERA or receive a TERA list exemption, and the criteria that 
must be met to receive an exemption from EPA review for certain types 
of R&D activities. Subpart F, which was an adaptation of Sec. 720.38, 
described the requirements for a test marketing exemption for 
microorganisms. Subpart G, which was entirely new, described the 
criteria that must be met in order to qualify for Tier I or Tier II 
exemptions for certain microorganisms in general commercial use. 
Subpart L, which was adapted from part 721, described additional 
procedures for reporting significant new uses of microorganisms. 
Although significant new use rules were not being proposed, it was 
intended that subpart M would list microorganisms and specific 
significant new uses when they were promulgated.
    In addition, EPA proposed to amend existing regulations regarding 
the collection of fees from submitters of notices under section 5 of 
TSCA (40 CFR part 700), to reflect the fee structure for the notices 
and applications that have been developed by these proposed rules. 
Additional amendments to parts 720, 721, and 723 were proposed to 
consolidate TSCA section 5 review of microorganisms into part 725.

III. Summary of Final Rule

    This final rule establishes all reporting requirements under 
section 5 of TSCA for manufacturers and processors of microorganisms 
subject to TSCA jurisdiction, that are manufactured for commercial 
purposes, including research and development for commercial purposes. 
The rule establishes a number of mechanisms for reporting to EPA, 
including a number of specific exemptions. Most of the exemptions 
create an alternative mechanism for reporting to EPA that reduces the 
amount of information to be reported. Certain of the research and 
development exemptions establish the conditions under which no 
reporting would be required.
    Manufacturers are required to report certain information to EPA 90 
days before commencing the manufacture of intergeneric microorganisms 
that are not listed on the TSCA Inventory. The rule establishes the 
mechanism for reporting this information. The rule also defines ``small 
quantities for research and development'' for microorganisms; the 
effect of which is to require section 5

[[Page 17912]]

reporting for certain research and development activities.
    Any manufacturer, importer, or processor of a living microorganism, 
who is required to report under section 5 of TSCA must file a Microbial 
Commercial Activity Notice (MCAN) with EPA, unless the activity is 
eligible for one of the specific exemptions. The general procedures for 
filing MCANs are described in subpart D of part 725 of the regulatory 
text.
    TSCA section 5 only applies to microorganisms that are 
manufactured, imported, or processed for commercial purposes. EPA has 
defined manufacture or process for commercial purposes as ``manufacture 
or process for purposes of obtaining an immediate or eventual 
commercial advantage.'' Whether an activity has an immediate or 
eventual commercial advantage is determined by indicia of commercial 
intent. Research and development activities are for commercial 
purposes, and thus subject to reporting, if tests are directly funded, 
in whole or in part by a commercial entity, when the researcher 
considers there to be an immediate or eventual commercial advantage. In 
addition, all post R&D activities are considered manufacture or 
processing for a commercial purpose.
    EPA has established two exemptions for new microorganisms, after 
the R&D development stage, which are being manufactured for 
introduction into commerce. In the Tier I exemption, if three criteria 
are met, manufacturers are only required to notify EPA that they are 
manufacturing a new microorganism that qualifies for this exemption 10 
days before commencing manufacture, and to keep certain records. A 
manufacturer is not required to wait for EPA approval before commencing 
manufacture. To qualify for the Tier I exemption, a manufacturer must 
use one of the listed recipient organisms and must implement specific 
physical containment and control technologies. In addition, the DNA 
introduced into the recipient microorganism must be well-characterized, 
limited in size, poorly mobilizable, and free of certain sequences.
    A manufacturer, who otherwise meets the conditions of the Tier I 
exemption, may modify the specified containment restrictions, but must 
submit a Tier II exemption notice. The Tier II exemption requires 
manufacturers to submit an abbreviated notice describing the modified 
containment, and provides for a 45-day period, during which EPA would 
review the proposed containment. The manufacturer may not proceed under 
this exemption until EPA approves the exemption.
    Rather than submitting a MCAN during research and development, 
manufacturers may qualify for one of several exemptions, or may choose 
to submit to EPA a TSCA Experimental Release Application.
    If a manufacturer is conducting research and development activities 
solely within a contained structure, the research may qualify for one 
of two exemptions. For contained research conducted by researchers who 
are required to comply with the NIH guidelines, EPA has established a 
complete exemption from EPA review and reporting and recordkeeping 
requirements. For all other manufacturers conducting contained research 
and development activities EPA has established a more limited 
exemption. The exemption specifies factors which the technically 
qualified individual must consider in selecting the appropriate 
containment. The manufacturer is required to keep records to document 
compliance with the containment requirements, but is exempt from all 
other TSCA section 5 reporting requirements. See Unit V.C.5. of this 
preamble.
    For researchers conducting small-scale field tests with 
Bradyrhizobium japonicum and Rhizobium meliloti, the final rule creates 
an exemption from EPA review, providing certain conditions are met. The 
field testing must occur on no more than 10 terrestrial acres; the 
introduced genetic material must comply with certain restrictions, and 
appropriate containment measures must be selected to limit 
dissemination.
    If a manufacturer does not meet the requirements for one of the 
exemptions discussed above, he or she may submit a TERA. The TERA is 
essentially an abbreviated MCAN submission for individual tests. EPA's 
review period is reduced to 60 days, although EPA may extend the period 
for good cause. EPA must approve the test before the researcher may 
proceed, even if the 60-day period expires. EPA's approval is limited 
to the conditions outlined in the TERA notice or approval.
    In addition, a manufacturer may submit a MCAN for any R&D activity. 
However, EPA expects that most researchers will instead choose to 
submit a TERA. In addition to the longer review period, EPA expects 
that, because of the limited information at the R&D stage, the Agency 
would likely issue a section 5(e) order to impose conditions to address 
the uncertainties, which would need to be modified each time the 
manufacturer wanted to vary the terms of the order.

IV. Summary of Major Changes in Final Rule

    The final rule adopts the provisions of the proposed rule with few 
revisions. EPA is adding to 40 CFR a new part 725, which applies TSCA 
section 5 requirements specifically to microorganisms. Subpart A of 
part 725 contains general provisions and applicability. The final rule 
retains from the proposal the definition of ``new microorganisms'' that 
are subject to TSCA section 5 reporting. ``New microorganisms'' are 
intergeneric microorganisms that are not already listed on the TSCA 
Inventory. ``Intergeneric microorganism'' is defined at Sec. 725.3. EPA 
has made some minor revisions to definitions in Sec. 725.3 related to 
scope of oversight.
    Subpart B of part 725 contains administrative procedures that have 
been adapted with little change from provisions in 40 CFR parts 720 and 
721. The provisions in the final rule have been adopted with minor 
changes from those proposed in 1994.
    Subpart C of part 725 contains requirements for claiming 
confidential business information (CBI). These requirements, which were 
adapted from provisions in part 720, have not been changed from the 
proposal, with the exception of the requirement relating to CBI claims 
in the TERA and other minor changes. Section 725.94(a)(2) has been 
modified to eliminate the proposed requirement for upfront 
substantiation of CBI claims in the TERA submission.
    Subpart D establishes the reporting program for new microorganisms 
manufactured or imported for distribution into commerce and requires 
submission of a MCAN 90 days prior to initiating manufacture or import 
of the new microorganism. This subpart codifies the requirements for 
information to be included in the MCAN at Secs. 725.155 and 725.160 and 
is promulgated with minor changes from the proposal.
    Subpart E establishes the exemptions from full MCAN reporting for 
R&D activities. At Sec. 725.205(b), EPA defines ``commercial purposes'' 
for R&D activities to include all R&D directly funded in whole or in 
part by a commercial entity, and all R&D activities, regardless of 
funding source, for which the researcher intends to pursue immediate or 
eventual commercial advantage.
    Subpart E establishes, at Sec. 725.232, a complete exemption from 
TSCA section 5 obligations for certain R&D activities conducted in 
contained structures and subject to regulation by another Federal 
agency. EPA establishes another

[[Page 17913]]

exemption from reporting requirements for R&D activities in contained 
structures which meet the requirements of Secs. 725.234 and 725.235.
    Subpart E also establishes at Secs. 725.238 and 725.239 the TERA 
exemption process for R&D activities, primarily those involving 
intentional environmental release. EPA has revised requirements in 
Sec. 725.239 to limit the antibiotic resistance markers that may be 
used in the microorganisms eligible for the TERA exemption.
    Subpart E codifies the requirements for information that must be 
included in the TERA at Secs. 725.255 and 725.260, and is promulgated 
with minor changes from the proposal. EPA has revised the requirements 
at Secs. 725.238(b)(3)(ii) and 725.255(e)(1)(vi) with regard to 
notification of State and/or local authorities.
    Subpart F contains the requirements for exemptions for test 
marketing activities. These requirements have been adapted, with little 
change, from provisions in part 720 and have only minor changes from 
the 1994 proposed rule.
    Subpart G establishes an exemption from MCAN reporting for certain 
microorganisms and places requirements on the recipient microorganism, 
the introduced genetic material, and the physical containment. Some 
changes have been made to requirements for specific eligibility 
criteria since the proposal. Section 725.421 contains the requirements 
for the introduced genetic material. Minor changes have been made to 
Sec. 725.421(d) to clarify the functional portions of toxin-encoding 
sequences that cannot be included in the introduced genetic material. 
Section 725.422 contains the requirements for physical containment. 
Section 725.422(b) has been revised to require controlled access to the 
structure. Section 725.422(e) has been modified to require submitters 
to document the effectiveness of the features used to minimize the 
microbial concentrations in aerosols and exhaust gases released from 
the structure.
    Subpart L establishes procedures for reporting significant new uses 
of microorganisms. These requirements have been adapted, with little 
change, from provisions in part 721 and have only minor changes since 
they were proposed in 1994.
    Subpart M is reserved for requirements for significant new uses for 
specific microorganisms; however, none are being promulgated in this 
rule.
    The regulatory text also amends existing regulations regarding the 
collection of fees from submitters of notices under section 5 of TSCA 
(40 CFR part 700), to reflect the fee structure for the notices and 
applications that have been developed by this rule. Additional 
amendments to parts 720, 721, and 723 consolidate TSCA section 5 review 
of microorganisms into part 725.

V. Discussion of Final Rule and Response to Comments

    In response to the proposed rule, EPA received 40 letters from the 
public during the comment period. Comments were received from industry, 
academia, professional and trade associations, government agencies, 
public interest groups, and individuals. While all commenters raised 
issues about specific aspects of the rule, several commenters indicated 
that they generally supported it. Some commenters had major concerns 
about the rule and suggested modifications that would have 
significantly changed the nature of the rule as it was proposed. EPA 
reviewed and considered all comments received on the proposed rule and 
prepared detailed responses to the comments. Copies of all comments 
received along with EPA's ``Summary of Public Comments and EPA's 
Response'' are available in the public docket for this rulemaking. A 
discussion of the final rule, including a summary of significant 
comments and EPA's responses follows.

A. Coverage of Microorganisms under TSCA

    EPA continues to believe that the TSCA section 3(2) definition of 
``chemical substance'' gives EPA authority to review microorganisms 
under TSCA. EPA is retaining its interpretation of ``new'' 
microorganisms as stated in the 1986 statement policy and the proposed 
rule. Under that interpretation, microorganisms resulting from 
deliberate combinations of genetic material from organisms classified 
in different genera constitute ``new'' microorganisms subject to 
section 5 reporting requirements. EPA terms such microorganisms 
intergeneric. For the purposes of this rule, EPA will treat mobile 
genetic elements, those elements of genetic material that have the 
ability to move genetic material within and between organisms, as 
follows: The term ``intergeneric microorganism'' includes a 
microorganism which contains a mobile genetic element which was 
originally isolated from a microorganism in a genus different from the 
recipient microorganism. Excluded from the definition of ``intergeneric 
microorganism'' are microorganisms which contain introduced genetic 
material consisting solely of well-characterized, non-coding regulatory 
regions from organisms in another genus. These terms are defined at 
Sec. 725.3.
    1. Intergeneric scope. EPA has decided to define ``new 
microorganisms'' as those microorganisms resulting from the deliberate 
combination of genetic material originally isolated from organisms 
classified in different genera because of the degree of human 
intervention involved, the significant likelihood of creating new 
combinations of traits, and the greater uncertainty regarding the 
effects of such microorganisms on human health and the environment. 
This approach, based on a taxonomic standard, both identifies a group 
of microorganisms whose behavior in the environment poses significant 
uncertainty, which therefore warrant regulatory review under TSCA 
section 5, and provides a way of defining ``new'' microorganisms under 
TSCA section 5.
    TSCA section 5 requires all manufacturers of new chemical 
substances to submit information to EPA 90 days before commencing 
commercial manufacture, to permit EPA to examine whether they may 
present an unreasonable risk of injury to health and the environment. 
As discussed at greater length in Unit II. of the Response to Comments 
Document, the rationale for the requirement was to have EPA attempt to 
resolve the uncertainties surrounding the class of new chemical 
substances--specifically, whether they were likely to cause 
unreasonable risks before they were introduced into the environment.
    When considering the various approaches that could be used to 
define a ``new'' microorganism for TSCA purposes, one important factor 
EPA took into account was the regulatory precedents established in 
compiling the inventory of existing chemical substances under section 
8(b) of TSCA. Any chemical substance not on the Inventory is ``new'' 
under section 5(a) of TSCA and is therefore subject to premanufacture 
reporting. Naturally occurring substances and substances derived from 
nature with limited human intervention are considered to be 
automatically included on the Inventory, and thus are not ``new.'' EPA 
concluded that microorganisms found in nature could also be considered 
not new because they occur naturally, without human intervention, and 
therefore, ``naturally occurring microorganisms'' are automatically 
listed on the TSCA Inventory, and are not subject to this rule.
    Second, EPA considered that modern biotechnology techniques permit 
genetic

[[Page 17914]]

material to be intentionally moved between and combined in disparate 
organisms. On occasion the genetic material combined would not be 
genetic material expressing traits possessed by both the donors of the 
genetic material and the recipients. In other words, the genetic 
material encoding these traits would not be commonly shared between the 
donor and recipient organisms. Microorganisms formed from genetic 
material not commonly shared by donors and recipients would have a 
significantly higher probability of exhibiting new traits or new 
combinations of traits compared to naturally occurring microorganisms. 
Some of the microorganisms developed through modern biotechnology may 
exhibit new or altered traits affecting, for example, their 
survivability, host range, substrate utilization, competitiveness with 
other organisms, or protein or polysaccharide production. The behavior 
of organisms expressing a new trait or new combinations of traits is 
thus less predictable and their probable behavior less certain. EPA 
chose to focus particular regulatory attention on microorganisms that 
have a higher potential for exhibiting a new trait or combinations of 
traits.
    EPA decided that a standard based on the taxonomic taxon of genus 
defined a class of sufficiently high probability of exhibiting a new 
trait or new combinations of traits to warrant review. Taxonomy is a 
system of orderly classification of organisms according to their 
presumed natural relationships. Since the organisms contributing 
genetic material to intergeneric microorganisms are, in general, more 
distantly related than the microorganisms contributing genetic material 
to intrageneric microorganisms (and thus less likely to have traits in 
common), intergeneric microorganisms have a higher probability of 
exhibiting a new trait or new combinations of traits and their behavior 
is therefore significantly less predictable than intrageneric 
microorganisms.
    A scope based on a taxonomic standard such as intergeneric has 
certain advantages. A taxonomy based scope relates directly to the 
potential of the resulting new microorganism to display a new trait or 
new combinations of traits, since organisms that share a close 
evolutionary ancestry are more likely to have traits in common than 
those that are more distantly related. In addition, the taxonomy 
standard is independent of the technology used to create the 
microorganism. A number of techniques may be used to produce 
intergeneric microorganisms. Any intergeneric microorganisms created by 
techniques developed in the future would also be subject to this final 
rule.
    Taxonomy reflects current scientific observations about phenotypic, 
and to a certain extent, genotypic, differences between organisms. 
Although subject to periodic revision within the scientific community, 
taxonomy is a common language used by scientists. Basing the standard 
for interpreting ``new'' for microorganisms on an existing system for 
categorizing organisms obviates the need to create another system for 
determining if a microorganism is subject to reporting under TSCA 
section 5. Taxonomy is understood by the regulated community and its 
use imposes little, if any, additional burden to determine whether a 
microorganism is new.
    For circumscribing what is new for TSCA section 5, microbial 
taxonomy is a relatively clear and objective criterion for scope of 
oversight and thus provides clarity for both the regulated community 
and the Agency for enforcement purposes. Taxonomic designations provide 
a widely available standard and point of reference. It is reasonable to 
expect a manufacturer to use the taxonomic literature and/or 
taxonomists to determine currently accepted names of organisms they 
wish to utilize. Once a manufacturer knows the genus of a 
microorganism, he or she can readily determine whether a microorganism 
is intergeneric and thus whether it is ``new'' within the section 5 
context.
    EPA recognizes that taxonomy, particularly microbial taxonomy, is 
subject to change and that new information concerning organisms' 
properties and relationships could alter taxonomic designations. In 
recent years, new tools have become available to microbial taxonomists 
which have allowed them to clarify phylogenic relationships among 
microorganisms. Some microbial genera are highly defined and consist of 
closely related members which are likely to share common information in 
their genetic material. However, other microbial genera may consist of 
members more closely related to microorganisms classified in other 
genera than to each other. While reorganizations could result in 
changes in taxonomic designations for some microorganisms in the short 
term, it should result in greater stability in the various taxa in the 
long term. EPA anticipates that as reclassifications occur in the 
scientific community, the intergeneric standard will become a better 
reflection of the probability of new traits or new combination of 
traits resulting from the deliberate combining of genetic material. 
However, even under current taxonomic designations, gene exchange is 
generally less likely to occur naturally among members of different 
microbial genera than among members of the same genus, and this 
suggests a new trait or new combinations of traits are more likely to 
occur when genetic material from microorganisms in different taxonomic 
genera are combined. Moreover, the probability of a new trait or new 
combination of traits occurring increases when the organisms combining 
genetic material are more distantly related; e.g., even among the 
microorganisms, bacteria classified in different genera are more likely 
to share common traits than bacteria and fungi, and bacteria classified 
in different genera are more likely to share traits than bacteria with 
plants and animals. While taxonomic reorganizations could affect the 
status, for TSCA purposes, of some microorganisms formed by combining 
genetic material from some relatively closely related microorganisms, 
the TSCA section 5 status of microorganisms formed by combining genetic 
material of more distantly related organisms is unlikely to be 
affected. These considerations suggest that while taxonomy may not be a 
perfect standard, its use is likely to capture for review those 
microorganisms with a higher probability of displaying new traits or 
new combinations of traits. EPA discusses in other parts of this 
preamble and in the Response to Comments document how it will 
accommodate within its regulatory structure reclassifications of 
microorganisms into new or different taxa.
    EPA believes that on whole, the intergeneric definition generally 
captures for review microorganisms with a higher potential for 
displaying a new trait or new combination of traits. While this 
approach does have some drawbacks, EPA believes that its procedures are 
sufficiently flexible to accommodate these drawbacks, and that the 
advantages to using the intergeneric definition outweigh the 
disadvantages.
    EPA includes the phrase ``originally isolated'' in the definition 
of intergeneric to clarify that genetic material belongs to the genus 
from which it was originally isolated or originally observed. For 
example, if a sequence of genetic material was originally introduced 
from microorganism A into microorganism B, subsequently reisolated from 
microorganism B to be combined in microorganism C, the manufacturer or 
developer must consider the genera of microorganisms A and C in 
determining the status of the microorganism

[[Page 17915]]

resulting from the second combining event described above.
    2. Mobile genetic elements. In the proposal (59 FR 45528), EPA also 
discussed mobile genetic elements (MGEs) and how it would apply its MGE 
policy to the interpretation of ``new'' microorganisms for the purposes 
of TSCA section 5. EPA has retained the policy and incorporated it in 
its definition of intergeneric microorganism. MGEs, which are elements 
of genetic material such as plasmids and transposons, may in nature 
move within or among organisms and may carry with them and transfer 
genetic material in addition to their own. MGEs, which are used as 
vectors for moving genetic material among organisms, may move across 
taxonomic boundaries and therefore are not a constant part of the 
genome of one particular taxonomic group or another.
    After publication of the 1986 policy statement describing EPA's 
intergeneric interpretation, several producers of microorganisms 
inquired about the status under TSCA of microorganisms containing MGE 
material. Therefore, it was necessary for EPA to develop an approach 
for addressing MGEs under the intergeneric interpretation. In keeping 
with its intergeneric definition which focused on the origin of the 
introduced genetic material, EPA decided that microorganisms would be 
considered intergeneric if they contained an MGE first identified in a 
microorganism in a genus different from the recipient microorganism 
genus. Microorganisms would be considered intrageneric, and not new, if 
the literature indicates the MGE was first identified in a 
microorganism in the same genus as the recipient. EPA has continued to 
use this policy regarding MGEs to assist in determining whether a 
microorganism is intergeneric.
    The issue of whether the MGE may be indigenous to the recipient 
genus is not considered in EPA's approach to determining whether the 
final microorganism is inter- or intrageneric. The major consideration 
is the source of the organism in which the MGE was first identified. 
The source of the organism in which the MGE was first identified may be 
determined by a search of relevant published scientific literature or 
by reviewing available data bases such as GENBANK. Such a literature or 
data base reference is often the first to name, and possibly describe, 
the MGE. Subsequent references postdating this first reference are 
frequently not relevant for determining the intergeneric status of the 
MGE, since after isolation an MGE is often transferred to a different 
taxon where it can be more easily maintained and studied. Although EPA 
recognizes that MGEs may occur in more than one genus in nature, EPA 
believes that for the moment, use of the source of the organism in 
which the MGE was first identified for classifying MGEs provides the 
most straightforward regulatory approach under its intergeneric 
definition. EPA will continue to use this approach until it can 
reevaluate the status of MGEs within an intergeneric standard in a 
future rulemaking. EPA has included a statement about MGEs in its 
definition of intergeneric microorganisms in this final rule.
    3. Well-characterized, non-coding regulatory regions. In the 1986 
policy statement and in the proposed rule, EPA excluded from the 
definition of intergeneric microorganisms, those microorganisms that 
resulted from the addition of intergeneric material that is well-
characterized and contains only non-coding regulatory regions such as 
operators, promoters, origins of replication, terminators, and 
ribosome-binding regions. Where only regulatory material is 
transferred, no distinctly new combinations of traits are introduced. 
Instead, quantitative changes in existing traits in the recipient 
microorganisms may occur. EPA recognizes that insertion of well-
characterized, noncoding regulatory regions may result in expression of 
previously cryptic regions. However, the genetic material in cryptic 
regions is present in the population and could be expressed in some 
members of the microbial population at any time naturally. A 
microorganism expressing such material as a consequence of insertion of 
non-coding regulatory regions would thus not be new under TSCA. 
Therefore, EPA believes that microorganisms formed through intergeneric 
transfer of well-characterized, non-coding regulatory regions should 
not be considered ``new'' microorganisms under TSCA section 5. EPA 
emphasizes that this exclusion applies only to intergeneric 
microorganisms that have resulted solely from the addition of well-
characterized, non-coding, regulatory regions. If the final 
microorganism contains any regions from organisms of other genera that 
do not meet this restriction, such as coding regulatory regions or any 
poorly characterized regions, the microorganism is considered new and 
is not eligible for the exclusion.
    In response to comments, EPA has revised some of its definitions at 
Sec. 725.3 relating to the intergeneric scope to provide greater 
clarity for the regulated community. The word ``introduced'' has been 
added to the second sentence in the definition of ``intergeneric 
microorganism'' to clarify that microorganisms which contain introduced 
genetic material consisting only of well-characterized, non-coding 
regulatory regions from another genus are not considered intergeneric 
for the purposes of TSCA section 5. EPA agrees with a commenter who 
suggested that the regulations should have a single definition of well-
characterized and that the definitions of ``well-characterized'' at 
Secs. 725.3 and 725.421(b) should be identical. To achieve this end, 
the phrase ``well-characterized, non-coding regulatory region'' would 
be deleted from Secs. 725.3 and ``well-characterized'' and ``non-coding 
regulatory region'' would be separately defined. Therefore, the 
definition of ``well-characterized, non-coding regulatory region'' is 
being deleted and definitions of ``non-coding regulatory region'' and 
``well-characterized'' are being added to Sec. 725.3. EPA agreed with 
the commenter's suggestion to use the language in Sec. 725.421(b) to 
define ``well-characterized.'' EPA developed the definition of ``non-
coding regulatory region'' based on language pertinent to the non-
coding aspect of the definition of ``well-characterized, non-coding 
regulatory region.'' EPA believes that it is necessary to specifically 
require that the regulatory regions be non-coding. As stated in the 
1986 policy statement and in the proposed rule, EPA excluded from the 
definition of intergeneric microorganisms, those microorganisms that 
solely contained intergeneric regulatory regions that are well-
characterized and non-coding. Such intergeneric material would not 
introduce distinctly new combinations of traits. Instead, only the 
level of expression of existing traits in the recipient microorganisms 
may be altered. By also including a restriction that the flanking 
sequences be non-coding, EPA is ensuring that persons will consider the 
nature of the flanking sequences associated with regulatory regions 
when determining their eligibility for the well-characterized, non-
coding regulatory region exclusion.
    In the proposed rule, EPA indicated that it may choose to 
reconsider its interpretation of ``new'' microorganism at a later time 
and in a separate rulemaking. Of the 17 comments received on scope of 
oversight, only 4 commenters strongly opposed the intergeneric scope 
and supported another approach, while 13 commenters expressed some 
level of support for intergeneric, albeit with some modifications. EPA 
believes that while

[[Page 17916]]

the intergeneric scope is not perfect, as one commenter noted, ``no one 
has proposed a clearly superior scope, despite years of discussion and 
debate.'' Therefore, EPA is retaining the intergeneric interpretation 
for the final rule. However, EPA appreciates the many useful 
suggestions made by commenters for refinement of the intergeneric 
interpretation and plans to consider at a later time modifications to 
the intergeneric interpretation, including issues related to the 
exclusion of well-characterized, non-coding regulatory regions and to 
the MGE policy. TSCA applicability and scope of oversight are discussed 
in detail in the proposed rule and in the Response to Comments document 
in Unit II.

B. Reporting General Commercial Use of Microorganisms

    1. MCAN and SNUR. The final rule incorporates many procedures that 
were originally developed for the TSCA section 5 program for 
traditional chemicals. Procedures from parts 720 (premanufacture 
notification (PMN)) and 721 (significant new use notification SNUN)) 
are being placed in the new part 725 with the minor modifications 
necessary to accommodate the specific characteristics of 
microorganisms. In lieu of the PMN or SNUN described in parts 720 and 
721, respectively, EPA is including in part 725 a requirement for 
submission of a MCAN by persons who intend to manufacture or import new 
living microorganisms, and by persons who intend to manufacture, 
import, or process microorganisms for a significant new use. Subpart D 
of part 725, which contains the MCAN requirements, is being promulgated 
without substantive revision. The MCAN process is discussed in the 
proposed rule and in the Response to Comments document in Unit III.A.
    EPA received general comments about the process, as well as 
specific comments about contract manufacturing, certain information 
requirements for the MCAN process, and the inclusion of requirements 
for byproducts. EPA is providing additional explanations and 
clarifications to address these concerns. Both the comments and EPA's 
responses are discussed in detail in the Response to Comments document 
in Unit III.A.
    In response to the commenters who stated that the information 
required to be submitted in the MCAN was confusing, burdensome, and 
open-ended, EPA notes that both the proposed and final rule require 
submission only of the information that is explicitly required to be 
submitted by TSCA section 5(b) and 5(d)(1). The purpose of the MCAN is 
to supply EPA with information necessary to identify and list the new 
microorganism on the TSCA Inventory and to determine whether the 
microorganism and the associated activities would pose an unreasonable 
risk of injury to human health or the environment. The MCAN information 
requirements closely parallel those for PMNs and differ only to the 
extent necessary to accommodate the specific characteristics of living 
microorganisms. Therefore, the introductory paragraphs in Sec. 725.155 
have been revised to more closely parallel the introductory language in 
Sec. 720.45, which contains the information requirements for the PMN. 
EPA has also revised Sec. 725.155(b) to explicitly include the 
statement that the submitter should include all reasonably 
ascertainable information that will permit EPA to make a reasoned 
evaluation of the health and environmental effects of the 
microorganism. EPA believes that the addition of the statement in 
Sec. 725.155(b) also addresses the commenter who requested that EPA 
relate the information requested to the data necessary to assess 
potential risk to human health and the environment.
    The proposed subpart L of part 725 incorporated the Significant New 
Use Rule (SNUR) provisions from part 721 with minor modifications to 
accommodate the specific characteristics of living microorganisms. EPA 
is promulgating subpart L in the final rule with minor revisions, 
primarily to clarify the relationship of subpart L to the other 
subparts in part 725. EPA has not yet proposed a SNUR for a specific 
microorganism. EPA has clarified its approach to microorganism SNURs in 
response to commenters. The SNUR for microorganisms is discussed in the 
proposed rule (59 FR 45552-53) and in the Response to Comments document 
in Unit III.B.
    2. Tiered exemption. EPA is establishing under TSCA section 
5(h)(4), the Tier I and Tier II exemptions for certain microorganisms 
meeting certain criteria. The criteria defining eligibility for the 
Tier I exemption address: (1) The recipient microorganism; (2) the 
introduced genetic material; and (3) physical containment conditions to 
minimize the numbers of microorganisms emitted from the manufacturing 
facility. For the Tier II exemption, only the first two of the Tier I 
criteria must be met. Manufacturers would select containment 
appropriate to minimize release of the microorganisms. EPA would review 
the appropriateness of the containment for the microorganisms in an 
expedited 45-day review. The requirements for the tiered exemptions are 
found in subpart G of part 725. In response to comments, EPA has made 
certain revisions to requirements for the introduced genetic material 
at Sec. 725.421 and for physical containment at Sec. 725.422. These are 
discussed below. The tiered exemption is discussed in detail in the 
proposed rule (59 FR 45545-50) and in the Response to Comments document 
in Unit III.C.
    a. General comments. EPA received comments on issues related to the 
overall approach to the tiered exemption. While EPA did not make 
substantive changes to the process for the Tier I and Tier II 
exemptions, EPA did make minor changes in Secs. 725.424 through 725.470 
to further clarify exemption requirements. In Unit III.C. of the 
Response to Comments document, EPA provided additional explanation of 
its rationale for development of the tiered approach.
    Some commenters indicated that it is ``excessive and unwarranted'' 
to require the submitter for a tiered exemption to certify that test 
data are being submitted as stated in Sec. 725.25(b). Another commenter 
stated that a 30-day review was not necessary and that companies 
working with organisms eligible for the Tier I exemption should simply 
document their eligibility in their records.
    EPA wishes to clarify how the certification statement at 
Sec. 725.25(b) applies to the tiered exemption. The first two 
sentences, where the company indicates that it intends to manufacture 
the microorganism identified in the submission and that all information 
is complete and truthful, are applicable to all submitters. However, 
the last sentence is only relevant to persons preparing either the MCAN 
which includes information requirements at Sec. 725.160 or the TERA 
which includes information requirements at Sec. 725.260. To reduce 
confusion, EPA has added a clarification to Sec. 725.424(b)(5). EPA 
inadvertently neglected in the proposed regulatory text, although the 
proposed preamble clearly describes procedures, to include the 
requirements at Sec. 725.424(b)(4) and (5) as requirements for the Tier 
II exemption at Sec. 725.455. Therefore, EPA has added those 
requirements as Sec. 725.455(e) and (f) in the final rule. Although 
Sec. 725.25(b) states that persons submitting exemption requests must 
submit the certification statement, EPA has repeated the requirement at 
Secs. 725.424(b)(5) and 725.455(f) for the convenience of submitters. 
The requirement at Sec. 725.455(e) was

[[Page 17917]]

inadvertently left out of the proposed rule; however, EPA does not 
believe that this requirement adds an additional burden, because 
submitters should already have information about waste disposal of the 
microorganisms.
    EPA agrees that EPA review is not required for the Tier I 
exemption, as EPA has already made the no unreasonable risk finding for 
microorganisms meeting the conditions of the exemption. EPA has 
structured the Tier I exemption such that EPA receives a one-time 
certification alerting EPA to the application of the exemption and to 
demonstrate that the submitter is complying with the criteria set out 
for the exemption. The certification contains no data for EPA to 
review. Once a person has sent in the certification required by 
Sec. 725.424, subsequent uses of the same recipient do not require 
additional certification under Sec. 725.424, as long as the 
manufacturer is continuing to comply with the introduced genetic 
material requirements of Sec. 725.421 and the containment requirements 
of Sec. 725.422. While EPA does not believe that an EPA review is 
necessary, EPA does believe that it is appropriate for EPA to be 
notified of which manufacturers are eligible for and utilizing the 
exemption. However, EPA also has decided that since the purpose of the 
certification is solely to inform EPA that persons are using the Tier I 
exemption, such notification is not needed 30 days in advance, and 10 
days in advance of manufacture or import is sufficient. Therefore, EPA 
has revised the requirement at Sec. 725.424(a)(4) to require submission 
of the certification to EPA at least 10 days before commencing initial 
manufacture or import of a new microorganism.
    b. Recipient microorganism. EPA received no substantive comments 
challenging EPA's approach to selecting recipient microorganisms for 
listing or questioning the eligibility of the 10 candidates proposed 
for listing. Therefore, EPA has not made substantive changes to its 
approach to selecting recipient microorganisms. Section 725.420 
continues to list the 10 microorganisms as eligible for use in the 
tiered exemption. Although EPA explained in detail in the proposal (59 
FR 45545-47) the considerations it evaluated in selecting candidate 
microorganisms for listing at Sec. 725.420, EPA provided commenters 
with additional explanation as to how six criteria are used together to 
determine a microorganism's eligibility for listing at Sec. 725.420. 
The recipient microorganism criteria are discussed in detail in the 
proposed rule (59 FR 45545-47) and in the Response to Comments document 
in Unit III.C.2.
    Some commenters were concerned about the effect of potential 
changes in microbial taxonomy on the microorganisms listed at 
Sec. 725.420. The risk assessments that EPA prepared for the 10 
microorganisms listed at Sec. 725.420 evaluated the hazards of the 
microorganisms as they were appropriately designated taxonomically in 
1994. Therefore, EPA believes that if in the future the name is changed 
for any of the 10 microorganisms currently listed in Sec. 725.420, 
persons would need to document that their microorganisms would have 
been classified in 1994 under the name listed in Sec. 725.420.
    EPA proposed the petition process at Sec. 725.67 to provide a 
mechanism for the public to propose additional candidates and provide 
the appropriate supporting information. As a general matter, EPA 
expects that petitions to add specific recipient microorganisms to the 
list at Sec. 725.420 will ideally be preceded by several MCANs before 
the necessary experience with and information on the microorganism have 
been accumulated to provide EPA with a starting point for determining 
whether the recipient should be listed as a candidate for the tiered 
exemption. EPA has revised the regulatory text for the petition process 
at Sec. 725.67 generally to clarify that the information required to be 
submitted in a petition will mirror the information requirements for 
the provision for which the exemption is being sought. With regard to 
the tiered exemption, EPA has indicated at Sec. 725.67(a)(3)(iii) that 
when applying to list a recipient microorganism for the tiered 
exemption under Sec. 725.420, persons should include information 
addressing the six criteria, which EPA will use to evaluate the 
microorganism for listing. EPA made the generic revision, because the 
petition process was designed to be used by anyone seeking to apply for 
a section 5(h)(4) exemption from full MCAN reporting under TSCA section 
5.
    One commenter asked EPA to clarify whether the microorganism 
Bacillus amyloliquefaciens would be considered a variant of the listed 
candidate Bacillus subtilis and thus eligible for the tiered exemption. 
EPA does not believe that Bacillus amyloliquefaciens can be subsumed 
under the exemption for Bacillus subtilis. B. amyloliquefaciens may 
have been considered a variant of B. subtilis in the past; however, by 
the time the risk assessment for B. subtilis was developed in 1994, B. 
amyloliquefaciens had been given separate species status (Ref. 1). 
Therefore, B. amyloliquefaciens is not synonymous with B. subtilis, and 
EPA is not including the former under the exemption for the latter.
    Another commenter asked that EPA add Pseudomonas fluorescens to the 
list at Sec. 725.420. After review of the information supplied by the 
commenter, and other information referenced in the Response to Comments 
Document in Unit III.C.2.b., EPA has concluded that the species P. 
fluorescens is not eligible for listing as a recipient microorganism 
under Sec. 725.420 at this time for the following reasons: its 
confusing taxonomic status; its lack of history of safe commercial use; 
and the potential of some strains currently classified as P. 
fluorescens to cause adverse effects on human health and the 
environment, particularly in relation to plant pathogenicity. EPA's 
review does not represent a full consideration of the species P. 
fluorescens, because sufficient information was not submitted. Thus EPA 
responds to the commenter's request as a rule comment and not a formal 
petition.
    c. Introduced genetic material. For the introduced genetic 
material, EPA identified four requirements in Sec. 725.421 which must 
be met to qualify for the Tier I or Tier II exemptions: the genetic 
material must be (a) limited in size, (b) well-characterized, (c) 
poorly mobilizable, and (d) free of certain sequences. EPA responds to 
comments on the criteria for the introduced genetic material within the 
context of the intergeneric scope. The terms in the final regulatory 
text for the tiered exemption refer to ``introduced genetic material'' 
and only the intergeneric portions of the introduced genetic material 
must meet the requirements at Sec. 725.421. Therefore, the requirements 
in Sec. 725.421 refer solely to the introduced genetic material which 
is derived from an organism classified in a different genus from the 
recipient microorganism. The introduced genetic material criteria are 
discussed in detail in the proposed rule (59 FR 45547-48) and in the 
Response to Comments document in Unit III.C.3.
    (i) Limited in size. The requirements for the ``limited in size'' 
criterion are set forth at Sec. 725.421(a), which states that 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, homopolymers, adaptors, transposons, insertion sequences, and 
restriction enzyme sites; (4) nucleotide sequences needed for vector 
transfer; and (5) nucleotide sequences needed for vector

[[Page 17918]]

maintenance. EPA discussed its rationale supporting the limited in size 
criterion in the preamble to the proposed rule (59 FR 45547).
    EPA is providing additional guidance for interpreting the ``limited 
in size'' requirements in this preamble and in the Response to Comments 
document in Unit III.C.3.a., but is not making changes to the 
regulatory text at Sec. 725.421(a). Commenters generally requested that 
EPA clarify which vector sequences would meet the criterion, including 
the status of certain sequences found in well-known, frequently used 
plasmids. In response, EPA is clarifying that it interprets requirement 
(3) above to allow the introduced DNA to contain vector material 
necessary for maintenance in and/or transfer to intermediate hosts, 
provided this vector material is not expressed in the intergeneric 
microorganism that will be manufactured under the tiered exemption. 
Such nonexpressed vector material should not change the behavior of the 
intergeneric microorganism. EPA also indicates that certain plasmid and 
phage vectors listed in Appendices E and I of the National Institutes 
of Health Guidelines for Research Involving Recombinant DNA Molecules 
(NIH Guidelines (59 FR 34496, July 5, 1994) (FR Doc. 94-16200)) (Ref. 
2) would meet the introduced genetic material criteria including the 
limited in size criterion.
    (ii) Well-characterized. The requirements for the ``well-
characterized'' criterion are set forth at Sec. 725.421(b) which states 
that well characterized means that the following have been determined 
for the introduced genetic material: (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); and (3) the presence or absence of associated 
nucleotide sequences where associated nucleotide sequences are defined 
as those ``needed to move genetic material, including linkers, 
homopolymers, adaptors, transposons, insertion sequences, and 
restriction enzyme sites.'' EPA discussed its rationale supporting the 
well-characterized criterion in the preamble to the proposed rule (59 
FR 45547).
    EPA is providing additional guidance for interpreting the ``well 
characterized'' requirements in this preamble and in the Response to 
Comments document in Unit III.C.3.b., but is not making changes to the 
regulatory text at Sec. 725.421(b). Commenters expressed concerns about 
what it means to know the functions of all products expressed by the 
structural genes, how to address open reading frames (ORFs) present in 
the introduced genetic material, what information is needed to 
determine whether upstream activator sequences meet the ``well-
characterized'' criterion, and whether complete genomic sequencing of 
the final construct is necessary to meet the well-characterized 
definition.
    EPA's intent in developing the ``well-characterized'' criterion was 
to ensure that the functions introduced with the genetic material were 
sufficiently understood to predict the likely behavior of the resulting 
microorganism. Because EPA defined a ``new'' microorganism as an 
intergeneric microorganism, it is the predicted effect of the 
intergeneric sequences on the phenotype of the recipient microorganism 
that must be evaluated. With regard to the functions of products 
expressed by introduced structural genes, manufacturers could rely, for 
example, on peer-reviewed literature on products of structural genes 
and/or the results of protein expression assays to characterize the 
function(s) of a gene product.
    Manufacturers must ensure, by evaluating ORFs and multiple reading 
frames, that unanticipated novel traits are not expressed by the 
intergeneric microorganism. ORFs must be assessed to determine whether 
a product other than the anticipated, desired product is likely to be 
expressed and to predict whether such a product(s), if expressed, would 
have an effect on the phenotype of the intergeneric microorganism.
    In determining the status of upstream activator sequences (UASs) 
with regard to the exemption at Sec. 725.421, manufacturers must first 
consider whether introduction of the UAS would create an intergeneric 
microorganism. For a UAS isolated from an organism in a different genus 
from the recipient microorganism, manufacturers should determine 
whether their UAS meets the requirements in the definitions at 
Sec. 725.3 for ``non-coding regulatory region'' and for ``well-
characterized.'' Microorganisms developed through the introduction of 
only UAS genetic material that is isolated from an organism in a 
different genus and that meets the above-noted definitions at 
Sec. 725.3, are excluded from the definition of ``intergeneric 
microorganism'' and therefore are not subject to the requirements of 
TSCA section 5.
    Manufacturers who wish to utilize the tiered exemption for 
microorganisms that contain both a UAS(s) and other genetic material 
isolated from an organism(s) in a different genus than the recipient, 
must, to meet the exemption requirements: (1) Ensure that the UAS meets 
the definitions of ``non-coding regulatory region'' and ``well-
characterized'' at Sec. 725.3; (2) ensure that the other introduced 
genetic material meets the requirements at Sec. 725.421(b); and (3) 
ensure that the other requirements of the Tier I or Tier II exemption 
are met.
    (iii) Poorly mobilizable. The requirements for the ``poorly 
mobilizable'' criterion are set forth at Sec. 725.421(c) which states 
that the probability that the introduced genetic material would be 
transferred to other microorganisms must be low, with a frequency of 
transfer of less than 10-8 transfer events per recipient. 
EPA discussed its rationale supporting the poorly mobilizable criterion 
in the preamble to the proposed rule (59 FR 45547-48).
    EPA is providing additional guidance for interpreting the ``poorly 
mobilizable'' requirements in this preamble and in the Response to 
Comments document in Unit III.C.3.c., but is not making changes to the 
regulatory text at Sec. 725.421(c). Some commenters requested 
clarification on the conditions under which the 10-8 
criterion should be measured. They also requested that EPA clarify the 
status with regard to the ``poorly mobilizable'' criterion of 
introduced genetic material located on the chromosome.
    EPA believes the 10-8 criterion, which is a standard 
established by NIH in its Guidelines (Ref. 2) and an important feature 
of the Good Industrial Large-Scale Practices (GILSP) criteria developed 
by the Organization of Economic Cooperation and Development (OECD) 
(Ref. 3), should be applied to the introduced genetic material under 
Sec. 725.421, because EPA is not restricting (aside from that under 
Sec. 725.421(d)) the source and function of the introduced genetic 
material. Therefore, EPA in order to make the finding that organisms 
meeting the other criteria at Sec. 725.400 present low risk, the 
``poorly mobilizable'' standard must be included in the criteria at 
Sec. 725.421. EPA believes that manufacturers can readily determine 
whether the introduced genetic material will meet the 10-8 
criterion. For many bacteria, most sequences introduced by transduction 
and transformation will a priori meet the 10-8 criterion. 
Therefore, a single mechanism of gene exchange, conjugation, will need 
to be considered and the introduced genetic material constructed to 
meet the 10-8 standard for that mechanism. EPA also 
clarifies that genetic material stably integrated into the chromosome 
with no functional transposons is likely to meet the 10-8 
criterion.

[[Page 17919]]

    (iv) Free of certain sequences. The requirements for the ``free of 
certain sequences'' criterion were set forth at proposed 
Sec. 725.421(d) which indicated that the introduced genetic material 
must not contain any part of the nucleotide sequences that encode 
certain listed toxins, which are polypeptides of relatively high 
potency. EPA discussed its rationale supporting the ``free of certain 
sequences'' criterion in the preamble to the proposed rule (59 FR 
45547).
    A commenter noted that the language in proposed Sec. 725.421(d), if 
taken literally, would ``preclude the use of DNA that codes for a pair 
of amino acids (or even a single one) if that sequence also occurs in 
any of these toxins.'' In order to clarify this point, the commenter 
suggested that the language be altered to state that the introduced 
genetic material must not contain a sequence ``encoding any active 
moiety of a toxin'' listed in Sec. 725.421(d).
    EPA is providing additional guidance for interpreting the ``free of 
certain sequences'' requirements in its Response to Comments document 
in Unit III.C.3.d., and is modifying the regulatory text at 
Sec. 725.421(d) to clarify its intentions. The introductory text of 
Sec. 725.421(d) has been modified to include the term ``functional 
portion of a toxin-encoding sequence.'' To assist submitters in 
interpreting the term ``functional portion'' of a toxin-encoding 
sequence described at Sec. 725.421(d), EPA provides a discussion of 
sequences that directly or indirectly contribute to toxic effects in 
human cells. For toxins that affect a cell's cytoplasmic functions, 
nucleic acid sequences that encode the ``functional portion'' of a 
toxin are those which encode either functional receptor binding or 
toxic domains of the toxin. For toxins that affect a cell's membrane, 
nucleic acid sequences that shall not be included in the introduced 
genetic material are those which encode the functional portion that 
allows target cell membrane disruption.
    EPA did not intend for the restriction on toxin-encoding sequences 
to be interpreted to mean that the presence of a nucleotide found in a 
toxin gene sequence on the list at Sec. 725.421(d) would preclude 
introduced genetic material containing that nucleotide from qualifying 
for the tiered exemption. EPA believes the likelihood of any 
significant risk resulting from incorporation of nonfunctional portions 
of a toxin gene into a recipient listed at Sec. 725.420 is low. EPA is 
also modifying the definition to emphasize that EPA is excluding 
specific toxin sequences and not source organisms, which are listed at 
Sec. 725.421(d) to identify the toxins.
    d. Physical containment. The proposal included the following 
containment requirements at Sec. 725.422 for the Tier I exemption: (1) 
The structure is designed and operated to contain the microorganism, 
(2) limit entry only to those persons whose presence is critical to the 
reliability or safety of the activity, (3) provide written, published, 
and implemented procedures for the safety of personnel and control of 
hygiene, (4) provide and document effectiveness of inactivation 
procedures to reduce microbial concentrations by at least 6 logs in 
liquid and solid wastes, (5) provide and document effectiveness of 
features to reduce microbial concentration by at least 2 logs in 
aerosols and exhaust gases released from the structure, (6) include and 
document systems for controlling dissemination of the microorganisms 
through other routes, (7) have in place emergency clean-up procedures. 
Most of the comments focussed either on (2), the limited entry 
requirement, or (4) and (5), the inactivation requirements. The 
physical containment criteria are discussed in detail in the proposed 
rule (59 FR 45548-49) and in the Response to Comments document in Unit 
III.C.4.
    (i) Limited entry requirement. Some commenters indicated that the 
limited entry requirement was too restrictive, given the low potential 
hazards posed by microorganisms used under the Tier I exemption 
criteria. Specifically, they stated that under that requirement, 
managers may be precluded from allowing administrative personnel, 
customers, school and other educational tours into the facility. It was 
not EPA's intention to constrain facility managers to this extent. 
Consequently, EPA recognizes that language at proposed Sec. 725.422(b) 
may have been stricter than was necessary. Neither the NIH Guidelines 
(Ref. 2) nor the OECD GILSP criteria (Ref. 3) have specific limited 
entry requirements for large scale uses of comparable microorganisms. 
Additionally, EPA's review of PMNs received for intergeneric 
microorganisms indicated that restricted entry was not common industry 
practice (Ref. 4). EPA agrees with the commenters who stated that given 
the low risk posed by the microorganisms eligible for the exemption, 
managers should have the discretion to allow administrative personnel, 
customers, and school and other educational tours into the facility. 
However, EPA also expects that managers will maintain appropriate 
containment, thereby controlling access and avoiding inadvertent 
exposure. Modification of the language of this requirement does not 
alter EPA's original determination that microorganisms that are 
eligible for and used under the conditions of the Tier I exemption will 
not present an unreasonable risk of injury to human health and the 
environment. Therefore, EPA has revised Sec. 725.422(b) to read 
``Control access to the structure.''
    (ii) Inactivation requirements. Some commenters indicated that with 
the limitations placed on the recipient microorganism and the 
introduced genetic material, quantitation of inactivation procedures 
was not necessary. The commenters stated that it would be necessary to 
modify existing equipment to sample off-gas as required and that an 
additional sample port would increase the potential for contamination 
and worker exposure. The commenters suggested that instead of numerical 
requirements, language be substituted that more generally required 
reduction of microorganisms in liquid and solid wastes and aerosols and 
exhaust gases. Other commenters stated that the numerical requirements 
for the inactivation procedures are too lenient. These commenters 
suggested that gases be vented through a HEPA filter or incinerated. 
They also recommended that the containment criteria be coordinated with 
the containment levels set out in the NIH Guidelines (Ref. 2).
    After considering comments regarding its inactivation requirements 
at proposed Sec. 725.422(d) and (e), EPA reviewed information submitted 
on physical containment and control technologies in PMNs it has 
received for intergeneric microorganisms between 1986 and 1995 (Ref. 
4). On the basis of that review, EPA has made the following 
determinations. EPA has decided to retain Sec. 725.422(d) which 
requires the use of inactivation procedures that reduce microbial 
concentrations by at least 6 logs in liquid and solid wastes. However, 
EPA has determined that it is appropriate to revise Sec. 725.422(e) to 
read ``Provide and document effectiveness of features to minimize 
viable microbial populations in aerosols and exhaust gases released 
from the structure.'' The physical containment criteria are discussed 
in detail in the Response to Comments document in Unit III.C.4.
    As indicated in the preamble to the proposed rule (59 FR 45548-49), 
EPA believed that it was appropriate to prescribe standards for 
minimizing the number of microorganisms emitted through the disposal of 
wastes, because a wide range of behaviors could be displayed by 
microorganisms eligible for the exemption and because EPA would not be 
reviewing MCANs on

[[Page 17920]]

microorganisms eligible for the Tier I exemption. EPA believes that the 
requirement for a 6-log reduction in the number of microorganisms is 
reasonable for inactivation of liquid and solid wastes and well within 
current industry practices. The 6-log reduction criterion represents a 
level of inactivation which can be validated. This standard gives a 
decrease in viable microbial populations so that at least 99.9999 
percent of the organisms resulting from the fermentation will be 
killed. EPA discusses the application of this standard under normal 
industry practices in the proposed rule (59 FR 45548-49) and in the 
Response to Comments document in unit III.C.4.b. An examination of PMNs 
for intergeneric microorganisms (Ref. 4) revealed that this criterion 
is readily achievable by manufacturers. The review of these PMNs also 
indicated that in the several cases where monitoring was conducted 
there were no detectable viable microorganisms in liquid and solid 
wastes after inactivation (Ref. 4). EPA believes that the 6-log 
reduction in viable microbial numbers in the liquid and solid wastes is 
a reasonable and demonstrable performance criterion ensuring an 
appropriate level of containment for the low risk microorganisms which 
would be eligible for the tiered exemption.
    As indicated in the preamble to the proposed rule (59 FR 45548-49), 
EPA believed that it was appropriate to require manufacturers to 
minimize the number of microorganisms emitted through the venting of 
gases. A wide range of behaviors could be displayed by microorganisms 
eligible for the exemption, and EPA would not be reviewing MCANs for 
microorganisms eligible for the Tier I exemption. In the proposal EPA 
indicated that a 2-log reduction in viable microorganisms per cubic 
foot of air between the headspace and the actual vent port was the 
appropriate standard. EPA chose this number based on an estimate of the 
numbers of microorganisms likely to be in the exhaust from an 
uncontrolled fermentor and common industry practice. EPA discusses the 
application of this standard under normal industry practices in the 
proposed rule (59 FR 45549) and in the Response to Comments document in 
unit III.C.4.b. Additionally, the 2-log reduction represented a 
somewhat less restrictive number than the reduction obtained with HEPA 
filter filtration (the reduction level required for the NIH Guidelines 
BL1-LS level (NIH, Appendix K, 1995) (Ref. 2).
    However, EPA received several comments pointing out the technical 
problems associated with the proposed 2-log reduction performance 
criterion. EPA agrees with the commenters that companies should not 
have to modify/retrofit their existing equipment nor jeopardize the 
sterility of their fermentations in order to validate that the number 
of microorganisms being released in the exhaust has been reduced by at 
least 2 logs relative to the microbial numbers in the fermentor gases 
in the headspace. EPA did not intend that retrofitting or any other 
burdensome engineering modifications would be necessary for those who 
wished to utilize the Tier I exemption. Rather, EPA had intended to 
develop requirements for this exemption that would impose performance 
standards for equipment already commonly used. In light of comments 
received, EPA has sought to modify its requirement to achieve its goal 
of having submitters demonstrate that the equipment or features 
normally employed in fermentation systems are effective in reducing 
numbers of viable microorganisms being vented in exhaust gases.
    As stated in the preamble and noted by commenters, industrial 
fermentations are not routinely run in an uncontrolled fashion, and 
thus the number of microorganisms potentially released into the gas 
phase and unrecovered is controlled. Additionally, an examination of 
PMNs for intergeneric microorganisms (Ref. 4) showed that all of the 
fermentations, which were operating under standard industry practices, 
were utilizing features which minimize the number of microorganisms 
released in the off-gases.
    For fermentations to operate optimally, vapor recovery systems are 
used to maintain the correct growth conditions for the microorganisms, 
e.g., correct molality in the fermentation broth must be maintained. 
Vapor recovery systems, by their nature, help to minimize the number of 
microorganisms exhausted from the facilities. EPA believes that it 
should allow some flexibility in the type of features manufacturers 
employ to minimize microbial releases as aerosols. A variety of 
fermentor equipment or features are commonly used by the industry such 
as demisters, wet scrubbers, cyclone separators, coalescing filters, 
and HEPA filters. These types of equipment reduce the number of 
microorganisms vented through exhaust gases from the fermentor. 
Moreover, as stated in the preamble (59 FR 45549), even if 
microorganisms are exhausted from the fermentor, their survival is 
likely to be limited due to the stress conditions of aerosolization, 
including shear forces, desiccation, and UV light exposure.
    Given the comments received on the feasibility of this requirement 
and the variety of methods used by PMN submitters to reduce microbial 
numbers in aerosols, EPA believes that a specific numerical performance 
standard is less appropriate for inactivation of aerosols than it is 
for inactivation of liquid and solid wastes. EPA agrees with commenters 
who asserted that the majority of microorganisms potentially released 
from the fermentation facility would be found in the liquid and solid 
wastes. EPA has prescribed a specific viable microorganism reduction 
standard for these materials. Therefore, EPA believes that if the new 
microorganism meets all of the other requirements of the Tier I 
exemption, it is sufficient to require use of validated methods for 
minimizing release of microbial concentrations in aerosols and exhaust 
gases without prescribing a specific numerical reduction in numbers. If 
manufacturers are conducting their quality assurance/quality control 
(QA/QC) monitoring to ensure proper performance of their fermentation 
equipment, EPA believes that the facilities would be meeting the 
requirement of Sec. 725.422(e). EPA has revised Sec. 725.422(e) to 
read: ``Provide and document effectiveness of features to minimize 
viable microbial populations in aerosols and exhaust gases released 
from the structure.'' Based on the above points and the results of the 
review of EPA's PMN experience, EPA believes that this requirement will 
ensure that the number of microorganisms released in fermentor off-
gases will be negligible and allow EPA to make the ``no unreasonable 
risk'' finding of section 5(h)(4).
    EPA does not agree with commenters who stated that a 2-log 
reduction for aerosols is too lenient. As discussed in the proposed 
rule (59 FR 45549), even if small numbers of microorganisms are 
released in fermentor exhaust gases, aerosolization is a stressful 
condition decreasing the survival of most microorganisms. Aerosolized 
bacterial cells are weakened by shear forces, and are subject to 
desiccation and exposure to UV light. Therefore, survival of 
aerosolized microorganisms is expected to be limited. Since organisms 
which are eligible as recipient microorganisms for the Tier I exemption 
are low risk, EPA does not believe it is necessary to impose more 
stringent conditions than a requirement that manufacturers minimize the 
numbers of microorganisms in fermentor off-gases.

[[Page 17921]]

    Several commenters suggested that EPA coordinate its containment 
criteria with those specified in the NIH Guidelines (Ref. 2). EPA 
considered use of the NIH Guidelines when it was developing the tiered 
exemption but found such an approach to be problematic. In particular, 
the NIH Guidelines may change through a process independent of EPA 
activities such that the Guidelines would no longer provide the 
appropriate criteria to support a TSCA section 5(h)(4) exemption. EPA 
has developed an approach at Sec. 725.422 based, in large part, on 
standards set forth in the NIH Guidelines and the OECD GILSP that allow 
EPA to make the finding that is required under TSCA section 5(h)(4). 
However, in considering the specific containment requirements of the 
current NIH Guidelines (Ref. 2), EPA could not find one level in 
Appendix K that EPA believed would be appropriate for the Tier I 
exemption. The NIH Good Large Scale Practice (GLSP) criteria that would 
be applicable to some, but not all, of the microorganisms listed at 
Sec. 725.420, do not require minimization of the numbers of 
microorganisms released in off-gasses. Biosafety Level 1-Large Scale 
(BL1-LS) criteria require the use of HEPA filters or their equivalent, 
a 3-log reduction, and therefore are more restrictive than EPA's 
original 2-log reduction requirement.
    In reconsidering its original requirement, EPA believes that the 
costs of retrofitting existing equipment as well as the increase in 
potential contamination and worker exposure that would accompany sample 
collection necessary to validate the 2-log reduction requirement are 
not justified for the low risk microorganisms eligible for the 
exemption. EPA has attempted to make its approach compatible with good 
practice in industry. Most of the requirements of Sec. 725.422 are 
analogous to NIH Guidelines requirements. In particular, companies who 
are in full compliance with the NIH BL1-LS requirements would also be 
in compliance with Sec. 725.422(e), although the use of HEPA filters or 
their equivalent is a more stringent requirement than Sec. 725.422(e).

C. Reporting R&D Activities of Microorganisms

    As discussed earlier in this preamble and in the proposed rule, 
TSCA section 5 generally requires notification to EPA at least 90 days 
prior to the manufacture and importation of new chemical substances and 
90 days prior to the manufacture, importation, and processing of 
designated chemical substances for significant new uses. TSCA section 
5(i) makes clear that only manufacturing, importing, and processing 
``for commercial purposes'' are subject to section 5 notification. TSCA 
section 5(h)(3) exempts entirely from notification under section 5 the 
manufacturing, importing, and processing of chemical substances ``only 
in small quantities (as defined by the Administrator)'' for R&D, 
subject only to the manufacturer, importer, or processor notifying (as 
prescribed by EPA) the persons involved in the R&D activity of any 
risks to health associated with the substance.
    As discussed in more detail below, for traditional chemical 
substances, EPA has defined ``small quantities'' for R&D to be those 
quantities ``not greater than reasonably necessary'' for the R&D 
purposes. However, EPA is adopting a different definition of ``small 
quantities'' for R&D for microorganisms, because living microorganisms 
may reproduce and increase their own volume or amount. The definition 
adopted in this final rule limits the section 5(h)(3) exemption from 
section 5 MCAN requirements to R&D activities that are adequately 
contained as set forth in Sec. 725.234.
    This narrower definition of ``small quantities'' means that R&D 
activities conducted outside the prescribed containment (including 
field tests) do not qualify for the section 5(h)(3) exemption and are 
subject to the MCAN requirement. However, EPA has created, under 
authority of TSCA section 5(h)(4), other exemptions that will reduce 
the reporting burden for persons conducting certain R&D activities that 
do not qualify for the complete exemption in section 5(h)(3). These 
activities are discussed below.
    Researchers, including those in academic institutions, may be 
subject to TSCA section 5 jurisdiction because, by creating or 
reproducing microorganisms in their R&D activities, they are 
``manufacturing'' or ``processing'' such microorganisms. Since many 
such R&D activities involving microorganisms will not qualify for the 
section 5(h)(3) exemption from MCAN reporting, it is important for 
researchers, including those in academic institutions, to determine 
whether their activities fit within the definition of ``commercial 
purposes'' and, thus, are subject to TSCA section 5 and the MCAN 
requirements at all. Because of the nature of microorganism R&D and the 
broad definition of ``commercial purposes'' discussed below, it is 
likely that many researchers, including some in academic institutions, 
will be subject to TSCA section 5 jurisdiction for the first time and 
will want to utilize the TERA and other exemption provisions to reduce 
the reporting burdens involved in their R&D activities.
    Each of the exemptions for R&D activities applies to specific types 
of activities. At the beginning of R&D, while the research is taking 
place in a laboratory subject to appropriate containment, the R&D 
activity may be fully exempt under the section 5(h)(3) exemption if the 
researcher complies with the conditions set out in the rule. Once the 
researcher decides to conduct research outside the contained setting, 
such as field tests, the researcher will need to utilize a different 
exemption, such as the TERA.
    1. TSCA jurisdiction. EPA did not propose any provisions that would 
alter the jurisdictional scope of section 5, i.e., whether the use or 
potential use of a microorganism would be subject to TSCA. However, EPA 
received comments asking for clarification regarding TSCA section 5 
coverage of R&D activities with microorganisms. A commenter requested 
clarification of EPA's statement that ``EPA would consider that R&D 
activities involving new microorganisms where researchers are unsure of 
the final use would be subject to TSCA section 5.'' Some commenters 
requested that EPA confirm that researchers working with new 
microorganisms for the purposes of developing products such as drugs 
and foods would not be subject to TSCA section 5.
    EPA did not intend to imply that researchers using microorganisms 
would automatically be subject to section 5 requirements, without 
consideration of whether the research was conducted for a commercial 
purpose. The commenters apparently misunderstood EPA's proposed 
preamble discussion, which was intended only to explain the analytical 
steps to follow in determining whether researchers would be required to 
file a TERA notice.
    Researchers attempting to determine potential TSCA section 5 
obligations for R&D activities would first ascertain whether the use or 
potential use of the microorganism is specifically excluded from TSCA 
section 5. Uses that are not specifically excluded are subject to TSCA. 
EPA anticipates that much R&D activity with microorganisms will not be 
subject to TSCA. If the research is conducted with the intention of 
developing a product, the use of which would be subject solely to the 
Federal Food, Drug, and Cosmetic Act (FFDCA), the research would not be 
subject to TSCA. For example, with regard to biotechnology companies 
engaged in development of drugs, TSCA

[[Page 17922]]

specifically excludes substances used in the production of foods, 
drugs, cosmetics and medical devices from TSCA jurisdiction. 
Microorganisms used in the production of foods, drugs, cosmetics and 
medical devices are similarly excluded from TSCA. However, researchers 
unsure of the final use or potential use, or who intend to develop a 
product, a use of which could be subject to either FIFRA or TSCA, will 
need to consider whether they are subject to TSCA. Further discussion 
of the comments and EPA's responses can be found in the Response to 
Comment document at Unit IV.A. If the research is subject to TSCA, 
researchers may be eligible for one of the exemptions discussed in 
Units IV.C. and E. of the Response to Comments document.
    2. Commercial R&D. The most substantial decision made in developing 
the final rule was selection of the definition of commercial purposes 
for R&D activities. This issue is discussed in detail in the proposed 
rule (59 FR 45537-39) and in the Response to Comments document in Unit 
IV.B.
    TSCA section 5(i) limits all section 5 screening to activities for 
commercial purposes. Research on traditional chemicals is not generally 
affected by the commercial purposes limitation, because EPA's current 
regulatory definition of small quantities for R&D using traditional 
chemicals (any amounts reasonably necessary for research) at Sec. 720.3 
effectively exempts most research with these chemicals from section 5 
review. However, because of the ability of microorganisms to reproduce, 
disseminate and spread, EPA believed that it was necessary to review 
these products at an earlier stage and therefore proposed an 
interpretation to address testing with microorganisms. Consequently, 
EPA developed a different small quantities definition for 
microorganisms and is imposing reporting and recordkeeping requirements 
on certain R&D activities. Researchers utilizing microorganisms, 
therefore, will need to consider whether their R&D activities would be 
considered commercial, and therefore subject to TSCA section 5 
requirements.
    During development of regulations on biotechnology over the past 
several years, EPA has received numerous public comments that differ 
substantially on how the Agency should apply the commercial purposes 
definition to research. Of particular concern has been the 
appropriateness of an EPA oversight system based on the status of an 
activity as commercial or noncommercial rather than on potential risk. 
Because of the past difference in public opinion, EPA proposed three 
approaches to defining what constitutes commercial activities: (1) 
Using indicia to determine commercial purposes; (2) presuming all 
environmental testing is commercial; and (3) presuming that all 
environmental research is commercial but offering an opportunity for 
researchers to rebut the presumption. Rather than indicating a 
preference, EPA discussed in the preamble the advantages and 
disadvantages of each approach and asked for public comment on which 
approach would be appropriate.
    Comments received on the proposed rule produced no prevailing 
opinion on how EPA should define ``commercial purposes'' for R&D. In 
considering this issue, EPA turned to its experience over the past 
several years responding to researchers who inquired about the status 
of their field tests under TSCA. EPA based its responses to those 
inquiries, in part, on its approach to traditional chemicals under 
TSCA. Under the TSCA section 5 program for traditional chemicals, EPA 
determines whether an activity is for a commercial purpose based on 
whether the purpose of the activity is to have an immediate or eventual 
commercial advantage. EPA found that determining the commercial status 
of research microorganisms based on indicia similar to those used for 
traditional chemicals functioned adequately. Therefore, EPA has decided 
that for this final rule when determining whether their R&D activities 
with microorganisms would be ``for commercial purposes,'' researchers 
will need to consider the indicia listed in Sec. 725.205(b).
    The indicia approach applies to R&D in laboratories and other 
contained structures as well as to intentional testing in the 
environment and is discussed in more detail below.
    Researchers who are attempting to determine whether their research 
would be for ``commercial purposes'' should consult Sec. 725.205(b). 
Under Sec. 725.205(b)(1) researchers would first consider whether any 
of the funding for the proposed research comes directly from a 
commercial source. Any direct industry involvement in or direct funding 
of an activity at a noncommercial institution is for commercial 
purposes. This would include the use of company funds to develop the 
microorganisms or the use of a company-provided microorganism in the 
research. If any portion of the research is funded directly by a 
commercial source, then the research is ``for commercial purposes.'' 
Thus, if any part of the research is funded by contract, joint venture, 
or other financial arrangement, with the purpose of eventually 
producing a commercial product, the research is subject to the 
requirements of section 5. For example, laboratory work or field tests 
conducted under a research contract between a company and a university 
or a researcher where patent rights or trade secrets are held by the 
company, would be considered commercial R&D.
    If researchers do not fall under Sec. 725.205(b)(1), they should 
next consider potential indirect indicators of commercial intent as 
reflected in Sec. 725.205(b)(2). They would need to consider, for 
example, whether the research is directed towards developing a 
commercially viable improvement of a product already on the market, or 
whether they are seeking commercial funding or a patent.
    If researchers do not fall within the scope of Sec. 725.205(b)(1) 
or (b)(2), their research may be considered noncommercial. For example, 
an outright gift from a company to a university or a researcher without 
the company directing or otherwise controlling the research for which 
the funds are to be used or the use to be made of the results of the 
research conducted, would not be considered direct funding under 
Sec. 725.205(b)(1). As such, the research conducted using such a gift 
would be considered noncommercial R&D, assuming the researcher also 
does not believe the microorganism has the potential to be developed as 
a commercial product in the future or intend to obtain an immediate or 
eventual commercial advantage as described under Sec. 725.205(b)(2). 
Therefore, if a researcher is planning to conduct laboratory work or 
field tests or other environmental testing using funds which were part 
of an outright gift from a company to the university with no strings 
attached, that research would be considered noncommercial R&D.
    If none of the funding or support for the laboratory work or field 
test or other environmental testing, including development of the 
microorganism, comes from a commercial source, then the researcher must 
consider whether he or she intends to pursue the development of the new 
microorganism as a commercial product in the future, should testing 
show potential commercial viability. The researcher is responsible for 
judging when commercial intent exists for his or her particular 
research project. EPA recognizes that in the initial stage of research 
projects, researchers may not envision an eventual commercial purpose 
for their microorganisms. However, if, during the course of their 
investigations, researchers determine

[[Page 17923]]

that their microorganism has a potential commercial use which they 
intend to pursue, they then become subject to the requirements of TSCA 
section 5 and this rule, and their further research activities must be 
in compliance with this rule. EPA has provided examples of research 
that has an immediate or eventual commercial advantage in the 
regulatory text at Sec. 725.205(b)(2)(i) through (iv). An example of 
``other evidence'' of a commercial application cited under 
Sec. 725.205(b)(2)(iv) would be if the researcher has engaged in 
serious discussions with a company concerning marketing or 
commercializing the microorganism if initial research is successful. If 
researchers have difficulty deciding whether their research is for 
commercial purposes, they are encouraged to consult EPA.
    The above approach represents a modified version of the indicia of 
commercial purposes approach discussed in the preamble to the proposed 
rule. EPA has adopted this modified version for the following reasons. 
All research conducted directly by a commercial entity is clearly for 
commercial purposes, as the court decided in The Dow Chemical Company 
v. EPA, 605 F.2d 673 (3d Cir. 1979). Consequently, if a business 
directly funds a research activity for potential product development, 
the activity is for commercial purposes, even if the research activity 
is conducted at an academic institution. EPA has chosen to focus on the 
source of funding for the specific laboratory work or field test or 
other environmental testing as the appropriate indicator of commercial 
intent, because EPA recognizes that it can be difficult to trace 
sources of funding at the institutional level and agrees with the 
commenter who stated that ``there is no logical basis for the assertion 
that commercial support of one narrowly defined project changes the 
fundamental academic nature of every other activity conducted elsewhere 
in the institution.''
    EPA's definition of commercial purposes is consistent with the 
current regulations for traditional chemicals, which define a 
commercial activity as one undertaken with the purpose of obtaining an 
immediate or eventual commercial advantage. For example, this is the 
definition in Sec. 720.3(r), which defines ``manufacture or import for 
commercial purposes,'' and Sec. 721.3, which defines ``process for 
commercial purposes.'' Consequently, EPA has adopted the idea in 
Sec. 725.3, which defines for microorganisms ``manufacture, import, or 
process for commercial purposes.'' Similarly, Sec. 720.30(i) provides 
that ``non-commercial research and development'' consists of activities 
conducted by academic, government, or independent not-for-profit 
organizations ``unless the activity is for eventual commercial 
purposes.'' EPA has developed a comparable exclusion for non-commercial 
R&D uses of microorganisms by including a definition of ``commercial 
purposes for research and development activities'' at Sec. 725.205(b). 
As noted above, this commercial indicia approach applies to R&D in 
laboratories and other contained structures, as well as to intentional 
testing in the environment.
    EPA's experience over the past several years responding to 
researchers inquiring about the status of their environmental research 
under TSCA indicates the following points. All of the researchers 
identified the sources of their funding for the particular experiments. 
Generally they were able to readily indicate whether they believed 
there was a future commercial application for the microorganism which 
they intended to pursue. In most cases where a company was directly 
funding field tests to be conducted at university sites, the company 
contacted EPA directly and took responsibility for preparation of the 
PMN. In one case, researchers were being funded by Federal agencies but 
were using company-owned microorganisms subject to a TSCA section 5(e) 
consent order. The company asked EPA to modify the consent order to 
allow the company to give the microorganisms to the researchers for use 
in their field tests. Although the company made the original request, 
the researchers submitted information about their field tests to EPA. 
Therefore, researchers should contact EPA if they are planning field 
tests involving intergeneric microorganisms supplied by a company. In 
most cases, a TERA would be required.
    In several cases where researchers contacted EPA regarding the 
status of their field tests, EPA found that field tests using 
intergeneric microorganisms were not subject to TSCA, because the field 
tests were being funded by other Federal agencies and the researchers 
did not foresee future commercial uses for their microorganisms. 
Finding that these field tests did not constitute commercial R&D under 
TSCA, EPA directed the researchers to the Federal agencies which were 
the primary funding sources for the field tests and suggested that 
researchers should, at a minimum, obtain reviews from these agencies 
under relevant authorities, including meeting the National 
Environmental Policy Act (NEPA) responsibilities of these other 
agencies.
    Although EPA has chosen in this final rule to follow an approach 
for ``commercial purposes'' similar to its approach for traditional 
chemicals, EPA recognizes that there are no differences in risk 
depending on funding source. EPA takes seriously its responsibilities 
to address risk and intends to pursue approaches laid out in the 
Coordinated Framework for Regulation of Biotechnology (51 FR 23302, 
June 26, 1986) to ensure an adequate network of oversight of R&D 
activities. To this end, EPA will work closely with other agencies, 
particularly NIH.
    3. Microorganisms eligible for the R&D small quantities exemption. 
TSCA section 5(h)(3) exempts from section 5 screening, chemical 
substances manufactured or processed in small quantities solely for R&D 
and directs EPA to define small quantities by rule. EPA's regulations 
for traditional chemicals at Sec. 720.3(cc) define ``small quantities 
solely for R&D'' as those quantities that are ``not greater than 
reasonably necessary for ...[R&D] purposes.'' This definition of small 
quantities for R&D has been appropriate for traditional chemical 
substances, because these chemicals do not have the ability to increase 
their own volume or amount. However, living microorganisms may 
reproduce and increase beyond the number initially introduced, may 
establish in the environment, and may spread beyond the test site. Once 
they are released into the environment or are no longer contained, 
there is no longer an assurance they will remain ``small quantities.''
    Therefore, EPA's definition at Sec. 725.3 of ``small quantities'' 
for microorganisms is restricted to microorganisms used under 
conditions that meet the requirements of Sec. 725.234, which are 
designed to reduce the probability of establishment by reducing the 
number and frequency of viable microorganisms emitted from a facility. 
The small quantities exemption for microorganisms is also referred to 
as the ``contained structures'' exemption, because Sec. 725.234(c) 
limits the exemption to R&D activities in contained structures.
    Most of the comments EPA received on its application of the section 
5(h)(3) exemption to R&D activities with microorganisms in contained 
structures requested clarification with regard to the use of research 
microorganisms in commerce, the use of genetic libraries, and 
coordination with the NIH Guidelines. None of the commenters provided 
EPA with new information

[[Page 17924]]

that would cause EPA to reconsider or change the basis for its decision 
to restrict the section 5(h)(3) exemption to microorganisms used under 
conditions meeting the requirements of Sec. 725.234. Consequently EPA 
has adopted the proposed regulatory text for this exemption with some 
revisions. The requirements for this exemption are found in the 
regulatory text in Secs. 725.232, 725.234 and 725.235. These issues are 
discussed in the proposed rule (59 FR 45539-42) and in the Response to 
Comments document in Unit IV.C.
    For purposes of clarification, EPA has modified requirements 
originally included in proposed Sec. 725.235. Most of the proposed 
language was adapted, with little revision, from the small quantities 
exemption for traditional chemicals at Sec. 720.36. Upon further 
reflection, EPA has determined that some of that language is not 
appropriate for microorganisms. Therefore, EPA has deleted proposed 
Sec. 725.235(a)(2), which provided an exemption from the small 
quantities notification requirements for R&D in a laboratory, and 
proposed Sec. 725.235(e), which related to impurities and articles. 
Additionally, the requirements at proposed Sec. 725.235(c), (d), and 
(f) have been moved to Sec. 725.205(d), (e), and (f), respectively, as 
these requirements apply to all R&D activities under subpart E. EPA has 
further revised Sec. 725.205(f) to specifically exclude microbial 
pesticides by referring to the microbial pesticide notification 
requirements that were promulgated in September 1994 (59 FR 45612).
    EPA disagrees with the commenter who stated that EPA had not 
justified the ``wholesale removal of the R&D exemption provided by 
Congress.'' TSCA section 5(h)(3) does not provide a complete exemption 
for all R&D, nor has EPA removed the statutory exemption wholesale. 
Rather, TSCA section 5(h)(3) exempts from section 5 reporting chemical 
substances manufactured or processed in small quantities for R&D and 
specifically directs EPA to define ``small quantities'' by rule. EPA 
has determined that the definition of ``small quantities'' applied at 
Sec. 720.3 to traditional chemical substances cannot be applied to all 
R&D activities involving microorganisms for the reasons discussed in 
the proposed rule (59 FR 45539-40).
    4. R&D subject to TSCA and another Federal agency. In the proposed 
rule, EPA discussed situations where R&D activities might be subject to 
both TSCA and another Federal authority. EPA suggested different 
approaches to dealing with overlapping jurisdiction, depending on 
whether the R&D activities were conducted in a contained structure or 
involved intentional environmental testing.
    EPA proposed a complete exemption from EPA-specific reporting under 
TSCA section 5(h)(4) for research on new microorganisms in contained 
structures, if the research is regulated or funded by a Federal agency 
which has agreed to abide by the NIH Guidelines.
    In the proposed rule (59 FR 45542-43), EPA discussed exempting from 
TSCA section 5 requirements the intentional environmental testing of 
new microorganisms, when another Federal agency has clear regulatory 
authority and EPA determines that the other Federal agency's review 
addresses criteria equivalent to those which would be evaluated under 
TSCA section 5. Specifically, EPA indicated that it was working with 
USDA/APHIS to develop an exemption from TSCA section 5 requirements for 
R&D field tests reviewed by APHIS under the Federal Plant Pest Act and 
the Plant Quarantine Act.
    Several commenters supported the proposal to exempt from EPA 
requirements those researchers who mandatorily comply with the NIH 
Guidelines. Some commenters stated that researchers who voluntarily 
comply with the NIH Guidelines should also be exempt from the TSCA 
section 5(h)(3) requirements. Some commenters specifically supported 
EPA's discussion of potentially deferring to other agencies' reviews 
and determinations, when appropriate, for intentional environmental 
testing of new microorganisms. It was requested that EPA clarify its 
relationship with USDA/APHIS. Some commenters suggested extension of 
EPA's proposal to defer to other Federal agencies.
    EPA has retained at Sec. 725.232(b) its complete exemption from 
TSCA section 5 obligations for research on new microorganisms in 
contained structures, if the researcher is receiving funds from another 
Federal agency which requires compliance with the NIH Guidelines. This 
includes all research, whether directly funded by an agency or not, at 
a university or institution that adheres to the NIH Guidelines on an 
institution-wide basis as a condition of receiving Federal funds. EPA 
developed this exemption to avoid duplicative oversight with other 
Federal authorities. Researchers who are complying with the NIH 
Guidelines voluntarily or through vehicles such as contracts or local 
regulations, will not be eligible for the exemption at Sec. 725.232, 
because their research is not being overseen by another Federal agency. 
However, as discussed further below, EPA believes that anyone who is 
complying with the NIH Guidelines should be able to meet the 
requirements of Secs. 725.234 and 725.235 with little difficulty.
    EPA agrees in principle with commenters who believe that, when 
consistent with the requirements of the statutes involved, products 
subject to another statute as well as to TSCA need only be regulated by 
one of those agencies. Presently, EPA has identified the Plant Pest Act 
and Plant Quarantine Act administered by USDA/APHIS as presenting some 
degree of overlapping jurisdiction with TSCA for microorganisms. At 
this time EPA and USDA do not know of any products subject to 
overlapping jurisdiction. Should such a situation arise, EPA will work 
with APHIS to develop a proposed exemption from TSCA section 5 
requirements for R&D field tests subject to overlapping jurisdiction. 
In the future, should other cases of duplicative oversight arise, EPA 
will work with the other agencies involved to develop an appropriate 
solution. These issues are discussed in the Response to Comments 
document in Unit IV.D.
    5. Requirements for small quantities/contained R&D exemption. EPA 
indicated in the proposed rule (59 FR 45540) that for those researchers 
who are voluntarily complying with, but are not subject to, the NIH 
Guidelines, the requirements of the R&D small quantities exemption at 
Sec. 725.234 could be met by having the principal investigator (PI) 
serve as the technically qualified individual (TQI) required by 
Sec. 725.234(b) and keep records indicating that they abide by and are 
following the NIH Guidelines for the specific TSCA-subject R&D 
activities. However, EPA proposed to rely on the experience and 
judgement of the TQI to select containment and inactivation controls 
appropriate to the microorganism(s) being utilized. In some cases, the 
TQI could find it appropriate to use NIH Guidelines, and in others, the 
TQI might not. EPA took this position, because EPA recognized that many 
different kinds of microorganisms displaying a wide range of 
characteristics could potentially be used in research and that the type 
of controls appropriate for one microorganism might have limited 
relevance to other microorganisms. This issue is discussed in the 
Response to Comments document in Unit IV.E.
    Several commenters indicated support for use of the NIH Guidelines 
and requested clarification and/or made suggestions concerning the 
relationship of the NIH Guidelines to the R&D small quantities 
exemption. While EPA considers the NIH Guidelines to provide

[[Page 17925]]

the primary standard for laboratory research, EPA continues to believe 
that it is appropriate to allow TQIs to have the option of relying on 
their experience and judgement in selecting appropriate containment as 
opposed to being forced to rely solely on the NIH Guidelines. In 
addition, not all TSCA-subject microorganisms will also be subject to 
the NIH Guidelines, since the Guidelines focus on research involving 
recombinant DNA (rDNA) molecules and EPA focuses on intergeneric 
microorganisms as ``new.'' Therefore, some researchers will need to 
rely for some activities on EPA's criteria at Sec. 725.234, since their 
activities will not be covered by the NIH Guidelines. In structuring 
its approach, EPA believes it has provided an appropriate measure of 
flexibility to researchers. Additionally, EPA believes that those 
researchers who currently comply with the NIH Guidelines, but are not 
eligible for the exemption under Sec. 725.232, nevertheless can comply 
with the requirements of Secs. 725.234 and 725.235 with little 
additional burden beyond that imposed by the NIH Guidelines.
    With respect to the requirement at Sec. 725.234(d)(2) for 
certification by an authorized official, EPA recognized in the proposal 
(59 FR 45540) that Institutional Biosafety Committees (IBCs) and 
similar committees are charged with assessing the containment selected 
by researchers. EPA encourages the active use of such committees and 
agrees that an authorized official may be an IBC chair. EPA also 
evaluated the comments on the burden imposed by recordkeeping for the 
R&D small quantities exemption. As EPA noted in the proposal, EPA 
believes that persons following the NIH Guidelines would keep records 
as part of normal procedures at an institution where IBCs are 
responsible for ensuring the safety of research. Such records are 
likely to be adequate for meeting the provisions at Sec. 725.234(d)(3). 
This issue is discussed in more detail in the Response to Comments 
document in Unit IV.E., which also provides a comparison of the NIH 
Guidelines and the requirements of Secs. 725.234 and 725.235.
    Several commenters suggested that EPA adopt the NIH Guidelines as a 
requirement for the R&D small quantities exemption. As discussed 
previously, EPA believes that it is more appropriate to show 
researchers how the use of the NIH Guidelines can fulfill the 
requirements of the R&D small quantities exemption and has included a 
comparison discussion in the Response to Comments document in Unit 
IV.E.1. In general, EPA expects that companies currently complying with 
the NIH Guidelines will also be able to satisfy the requirements of the 
R&D small quantities exemption. Although the NIH Guidelines do not 
explicitly state that documentation of the notification is required, 
the requirement for such documentation can be readily inferred in 
section IV. of the NIH Guidelines. Because TSCA explicitly requires 
such notification, researchers may still need to verify that the 
documentation maintained pursuant to the NIH Guidelines includes 
documentation of the notification as specified in Sec. 725.235(c)(1).
    Like the NIH Guidelines, EPA's regulations cannot anticipate every 
research situation. Therefore, using the comparison of the NIH 
Guidelines and the requirements of Secs. 725.234 and 725.235 as 
guidance, researchers subject to TSCA section 5 and complying with the 
NIH Guidelines should evaluate their specific research situation to 
determine whether their use of the Guidelines also fulfills the 
requirements of Secs. 725.234 and 725.235.
    6. Exemptions from TERA reporting for certain R&D activities 
conducted outside a structure. In the proposed rule, EPA discussed a 
process for exempting small-scale field tests of certain microorganisms 
from TERA reporting. To qualify for the exemption, certain criteria 
regarding the recipient microorganisms, the source(s) and 
characteristics of the introduced genetic material, and the conditions 
of use would need to be met. EPA proposed certain strains of 
Bradyrhizobium japonicum and Rhizobium meliloti as candidates for 
exemption from TERA reporting, based on EPA reviews of voluntary PMNs 
for these microorganisms submitted under the 1986 Policy Statement and 
field test data generated in these field trials. In response to 
comments, EPA has modified some of the specific conditions for the 
exemption. Some commenters expressed concern about EPA's proposal to 
exempt strains containing antibiotic resistance markers from any 
source. EPA has determined that for the exemption described at 
Sec. 725.239, it will follow the conservative course of only allowing 
use in B. japonicum and R. meliloti of those markers EPA has reviewed 
for use in these microorganisms. This approach would ensure that the 
probability of presenting unreasonable risk would be low for each 
antibiotic resistance marker. The regulatory text at 
Secs. 725.239(a)(2)(ii)(A)(1) and 725.239(b)(2)(ii)(A)(1) has been 
modified to limit structural genes encoding marker sequences to those 
encoding resistance to the aadH gene, which confers resistance to 
streptomycin and spectinomycin, in these microorganisms. Based on EPA's 
analysis of use of this marker in rhizobia, and including consideration 
of the advice of the January 4, 1995 BSAC Subcommittee, the use of 
streptomycin and/or spectinomycin resistance markers in B. japonicum 
and R. meliloti currently meets this requirement of the exemption.
    EPA recognizes that the exemption at Sec. 725.239 is narrow and may 
only apply to very few research projects. It may be the case in the 
early years of the TERA program that TERA exemptions are narrowly 
written to apply to specific microorganisms that have completed TERA 
review. However, EPA hopes that in the longer term as EPA gains greater 
experience reviewing intergeneric microorganisms for environmental 
uses, broader exemptions can be written. To that end, EPA has placed 
general requirements for the TERA exemption in Sec. 725.238 and will 
use Sec. 725.239 to list certain microorganisms for the exemption and 
the specific conditions of use as needed.
    7. TERA reporting process. Under section 5(h)(4), EPA proposed to 
conditionally exempt from MCAN notification certain R&D activities 
involving new microorganisms. The exemption is conditional, since 
researchers must submit a TERA, an abbreviated notification. Due to the 
availability of other exemptions for R&D activities discussed in this 
preamble, EPA expects that the TERA will be used primarily for 
environmental research. In the proposed rule (59 FR 45535), EPA 
indicated that its goal was to review TERAs in 60 days, but that for 
good cause, EPA could extend the initial TERA review period by an 
additional 60 days, for a total of 120 days. This condition, the 
information requirements for submitters, and the TERA approval process 
have not been changed from the proposed rule. This exemption is 
discussed in the proposed rule (59 FR 45535-36, 45543-44) and in the 
Response to Comments document in Unit IV.G.
    EPA received some comments supporting the TERA process. Other 
commenters who opposed the use of the TERA process and stated that some 
of the information requirements were too extensive, also stated that 
specific monitoring data should be required. EPA has made minor 
revisions to the TERA requirements at Secs. 725.250 through 725.288. 
Issues raised about state coordination are discussed in the next 
section.
    EPA believes that it is necessary to establish a review and 
approval process

[[Page 17926]]

specifically for R&D activities involving environmental release. While 
many field tests of new microorganisms will be determined to pose low 
risks, this assumption cannot be made for field tests in general, and 
thus EPA finds some type of review is warranted. However, EPA 
recognizes that full MCAN reporting also may not be warranted. 
Therefore, EPA has chosen to develop a review and approval process 
specifically tailored to address R&D.
    EPA believes that the information requirements proposed for the 
TERA are appropriate. EPA must have sufficient information to evaluate 
the health and environmental effects of a planned field test. However, 
because a variety of microorganisms are potentially subject to TSCA, 
the requirements indicated in Sec. 725.255 are necessarily broad. Not 
all of the requirements are equally applicable to all microorganisms. 
Submitters are encouraged to consult with EPA prior to preparing TERAs, 
so that appropriate information needs and concerns may be identified.
    EPA has made minor changes to the regulatory text at Sec. 725.270 
to clarify that EPA is approving or denying the TERA. Therefore, the 
term ``TERA agreement'' which was used in the proposed rule has been 
changed to ``TERA approval.'' In addition to approving or denying the 
TERA, EPA may provide, in the TERA approval, conditions under which the 
R&D activity described in the TERA must be conducted in order for EPA 
to make the TSCA section 5(h)(4) finding that the R&D activity will not 
present an unreasonable risk to health or the environment. During the 
TERA review period, EPA may identify issues that need further 
information before EPA can give its approval for the R&D activity to 
proceed. EPA or the submitter may suspend the review period, if 
necessary. When EPA approves a TERA, the submitter must conduct the R&D 
activity only as described in the TERA, and any amendments to the TERA, 
and under any conditions specified by EPA in its approval of the TERA.
    8. Options for oversight of R&D activities. As discussed above, EPA 
proposed an approach for oversight of R&D activities which included a 
variety of exemptions from the full 90-day reporting process required 
for general commercial use activities. EPA's goal was to provide a 
flexible process which tailored oversight to the level of risk. EPA 
asked for comment on its R&D exemptions, all of which have been 
discussed above, and indicated that the public could suggest other 
options for consideration. Options for oversight suggested by the 
commenters are discussed in the Response to Comments document in Unit 
IV.H. For a variety of reasons, EPA concluded that the alternatives 
suggested would not adequately permit EPA to fulfill its statutory 
duties under TSCA section 5.
    Some commenters, while indicating that the R&D exemptions were 
comprehensible, did not believe that level of oversight correlated to 
level of risk. EPA disagrees with comments that the level of oversight 
imposed in its R&D exemptions is not correlated to level of risk. EPA 
discusses its view of the relationship between risk and the TSCA 
definition of ``new microorganism'' in Unit II.D. of the Response to 
Comments document. EPA has chosen to implement its R&D oversight in a 
manner which distinguishes between R&D activities in contained 
structures and R&D activities involving intentional release to the 
environment because of the greater overall potential in the latter case 
for survival, dissemination, and exposure to the microorganisms. Within 
this broad structure, EPA has developed several exemptions which 
recognize the differing risk potentials presented by different settings 
and organisms. These exemptions have been discussed above and are 
discussed in greater detail in Units IV.C. through G. of the Response 
to Comments document.
    In the proposed rule (59 FR 45536-37), EPA briefly discussed an 
alternative exemption for certain R&D releases. This alternative would 
contain requirements for documentation and recordkeeping by a TQI and 
certification by an authorized official. EPA is not finalizing this 
option at this time. However, EPA plans to propose an exemption along 
these lines at a later date to allow the public an opportunity to 
comment on the new information on which EPA is relying to support the 
exemption.

D. Other Issues

    1. Microorganism definition. In the proposed rule (59 FR 45550-51), 
EPA defined ``microorganisms'' in Sec. 725.3 as those organisms 
classified under the 5-kingdom system of Whittacker (Ref. 5) in the 
kingdoms Monera (or Procaryotae), Protista, and Fungi, the Chlorophyta 
and the Rhodophyta of the Plantae, and viruses and virus-like 
particles. Therefore, this definition includes, but is not limited to, 
bacteria, protozoa, fungi, mycoplasmas, mycoplasma-like organisms, 
spiroplasmas, microphytoplanktons, green and red algae, viruses, and 
virus-like particles (e.g., viroids, satellites, and virusoids). Should 
new categories of organisms within the Monera, Protista, Fungi and the 
Chlorophyta and Rhodophyta of the Plantae be identified, these would 
also be considered microorganisms under this definition.
    EPA proposed to treat viruses of other microorganisms (also termed 
phages) as MGEs. EPA's MGE policy is discussed in the proposed rule (59 
FR 45528) and in Unit II.D. of the Response to Comments document. In 
the proposed rule, EPA indicated that it was not able to identify uses 
of viruses of macroorganisms that might be subject to TSCA. EPA asked 
if it was appropriate to apply the intergeneric interpretation to 
viruses of macroorganisms if TSCA uses for such viruses were 
identified.
    Commenters thought the proposed definition of ``microorganism'' was 
reasonable and included the appropriate organisms. Thus, EPA will 
retain the definition of ``microorganism'' as discussed in the proposed 
rule and found in the regulatory text in Sec. 725.3. EPA has modified 
the definition to clearly indicate in the regulatory text that EPA is 
using the 5-kingdom classification of Whittacker. Additionally, as 
discussed in the proposal, EPA will treat phages as MGEs. No commenters 
identified current or imminent TSCA uses of viruses of macroorganisms. 
Therefore, EPA believes the best use of limited resources would be to 
develop an approach under TSCA for viruses of macroorganisms in the 
future if TSCA uses are identified. The definition of microorganism is 
discussed in the Response to Comments document in Unit V.A.
    2. TSCA Inventory. EPA described in the proposed rule (59 FR 45551-
52) how it planned to explicitly list microorganisms on the TSCA 
Inventory and the rationale for the proposed listing. EPA proposed to 
identify microorganisms on the Inventory using a taxonomic designation 
and a consistent set of supplemental information on phenotypic and 
genotypic traits necessary to identify the microorganism as precisely 
as possible. Additionally, EPA indicated that it was considering 
requiring that microorganisms listed on the Inventory be deposited in a 
recognized culture collection.
    In the proposed rule, EPA advised manufacturers and importers of 
any of the 192 microorganisms reported in 1978 for the initial TSCA 
Inventory that EPA planned to remove from the Inventory the explicit 
listing of these microorganisms. EPA believed that most of these 
microorganisms are not intergeneric; therefore they would be 
automatically included on the Inventory

[[Page 17927]]

and do not need to be explicitly listed. EPA asked manufacturers and 
importers of these microorganisms to inform EPA if any of the 
microorganisms were intergeneric and should not be removed from the 
Inventory.
    In response to EPA's request for comments on developing a 
requirement for culture collection deposit, several commenters strongly 
opposed the development of any requirement for deposit of a 
microorganism in a culture collection. One commenter was concerned 
about the effect that an EPA requirement would have on patent 
protection. Others believed that such a requirement would be 
unnecessary and onerous at the R&D stage. EPA has considered the 
concerns raised by commenters who oppose the culture collection 
requirement and has decided that deposit of new microorganisms in 
recognized culture collections is not necessary. Therefore, EPA has not 
made this a requirement for microorganisms subject to TSCA section 5 
reporting.
    Commenters asked that EPA clarify the type of taxonomic designation 
to be used for Inventory listing and indicate how revisions to taxonomy 
would be accommodated on the Inventory. Others asked EPA to clarify 
what is ``new'' under TSCA, particularly with respect to minor changes 
made during strain improvement of microorganisms already listed on the 
Inventory. EPA agrees that Inventory listing for intergeneric 
microorganisms is more complex than listing for most traditional 
chemicals. As indicated above, EPA plans to consider modifications and 
clarifications to its intergeneric interpretation in the future. Future 
modifications to the intergeneric interpretation will also affect how 
microorganisms are listed on the Inventory. A subcommittee of EPA's 
BSAC, which met on July 22, 1991, when questioned on EPA's proposed 
approach to Inventory listing for microorganisms, suggested that EPA 
continue on a case-by-case basis and gain additional experience before 
finalizing its requirements for Inventory listing. Therefore, EPA 
believes it prudent to defer a fuller development of Inventory listing 
for microorganisms until it has considered modifications to the 
intergeneric interpretation and gains additional experience. Meanwhile, 
EPA will use a case-by-case approach to Inventory listing for new 
microorganisms. Inventory issues are discussed in the Response to 
Comments document in Unit V.B. EPA has provided some clarification 
regarding use of taxonomy in the Response to Comments document in Unit 
II.D. Additional guidance on Inventory listing may also be found in the 
proposed rule preamble (59 FR 45551-52).
    Commenters requested that EPA provide a ``grandfather'' period by 
opening up the Inventory for 1 year after the final rule is published 
to allow products currently in commerce to be listed. One commenter 
requested that intergeneric products currently in commerce be 
automatically placed on the Inventory. EPA disagrees with the 
commenters who believe that a ``grandfather'' period is necessary. 
Since the publication of the 1986 Policy Statement in June 1986, EPA 
has required PMN reporting for general commercial use of intergeneric 
microorganisms subject to TSCA. Although different scopes of oversight 
have been discussed in the intervening years, the Policy Statement has 
remained in effect all that time. Therefore, EPA believes that the 
public has had sufficient notice of its program and that intergeneric 
microorganisms currently in commerce and being used for TSCA purposes 
should already have been reported to EPA.
    In response to the EPA proposal to delist 192 microorganisms 
currently listed on the Inventory by genus and species only, commenters 
discussed their concerns. One commenter stated that there was no 
information about the phenotypic characteristics of these strains or 
about any introduced DNA. EPA wishes to clarify its position on 
microorganisms currently listed on the Inventory. These microorganisms 
can be divided into two groups: (1) Those reported to the initial 
Inventory in the late 1970s, and (2) those listed after EPA's review of 
PMNs and receipt of Notices of Commencement to manufacture. EPA has no 
concerns about the Inventory status of the second group, because these 
microorganisms were all reported to EPA under the 1986 Policy Statement 
and therefore are intergeneric and are appropriately explicitly listed. 
The listings for these microorganisms include descriptive information 
to specifically identify them beyond the genus and species 
designations.
    Such is not the case for the first group, the 192 microorganisms 
reported for the initial Inventory in the late 1970s. As one commenter 
noted, these microorganisms are primarily listed by genus and species. 
EPA believes that most of these microorganisms are naturally occurring 
or have been modified by methods that do not involve the introduction 
of DNA from an organism in another genus and thus in many cases would 
not need to be explicitly listed. To confirm this assumption, EPA 
requested comment from persons manufacturing or importing any of the 
192 microorganisms. No comments were received on the status of these 
microorganisms. EPA wishes to ensure that all microorganisms which are 
explicitly listed on the Inventory are intergeneric and are described 
in a consistent manner. Therefore, EPA has concluded that the 192 
microorganisms are not intergeneric and, thus, are automatically on the 
Inventory under Sec. 725.8(b). EPA will remove the explicit listings 
from the Inventory in a separate action under the authority of TSCA 
section 8(b).
    3. Confidential Business Information. EPA proposed to require 
upfront substantiation of confidential business information (CBI) 
claims in all submissions for general commercial uses of 
microorganisms. Under the proposal, anyone submitting a MCAN, a Test 
Marketing Exemption (TME), Tier I certification, or a Tier II exemption 
request would be required to substantiate CBI claims at the time of 
submission. With respect to upfront substantiation for TERAs, EPA 
proposed two options and asked for public comments on both. Option 1 
would have required upfront substantiation of all CBI claims in TERAs. 
Option 2 would not have required upfront substantiation of CBI claims 
in TERAs, but would only require CBI substantiation after EPA received 
a Freedom of Information (FOIA) request.
    One commenter asked for additional clarification of EPA's CBI 
policy for microorganism submissions. Two commenters supported EPA's 
proposal to require upfront substantiation of CBI claims for 
submissions for both research and general commercial use. However, most 
commenters opposed upfront substantiation of CBI claims in R&D 
submissions, indicating that the requirement was too burdensome for 
R&D, especially because it was important to have proprietary protection 
for R&D activities. Some commenters specifically opposed upfront 
substantiation of CBI claims in submissions for R&D submissions only. 
Others opposed upfront substantiation of CBI claims in any 
microorganism submission, arguing that EPA's approach to substantiation 
of CBI claims in microorganism submissions should not differ from EPA's 
approach to substantiation of CBI claims in traditional chemical 
submissions.
    Considering the competing interests in the comments received and 
the burden imposed on industry, EPA has decided not to require upfront 
substantiation of CBI claims in TERAs

[[Page 17928]]

but will retain the upfront substantiation requirement for CBI claims 
in MCANs, TMEs, Tier I certifications, and Tier II exemption requests. 
In the past several years, submitters of voluntary PMNs for field tests 
of new microorganisms have claimed very little, if any, CBI. However, 
if, in the future, EPA finds that CBI claims have increased in TERAs 
and that insufficient information is available to the public during the 
shorter TERA review period, EPA may find it necessary to reconsider the 
decision not to require upfront substantiation of CBI claims in TERAs. 
At this time, EPA has revised the regulatory text at Sec. 725.94(a)(2) 
to delete the requirement for upfront CBI substantiation. In the case 
of general commercial use submissions, EPA believes that the upfront 
substantiation requirement for CBI claims will impose little burden on 
submitters of MCANs, TMEs, Tier I certifications, and Tier II exemption 
requests. Because persons preparing these submissions are ready to put 
their products on the market, they will have a greater understanding of 
the products and any CBI issues and, therefore, should be able to 
justify why it will continue to be necessary to keep certain 
information confidential. In addition, given the shorter review period 
for TMEs and Tier II exemption requests, sufficient information may not 
be made available to the public if upfront substantiation of CBI claims 
is not required. In particular, EPA may not be able to comply with all 
deadlines if a FOIA request is received.
    4. Antibiotic resistance markers. EPA did not establish a general 
policy for addressing antibiotic resistance markers as part of its 
proposed rule. Use of antibiotic resistance markers was only discussed 
as part of the exemption from TERA reporting proposed for certain 
modified strains of Bradyrhizobium japonicum and Rhizobium meliloti at 
proposed Sec. 725.239. Although EPA only discussed the use of 
antibiotic resistance markers as part of its proposal for exempting two 
specific microorganisms from TERA reporting, EPA also received comments 
addressing more generally the use of antibiotic resistance markers. As 
discussed above, EPA has responded to comments on the TERA exemption, 
including revising the regulatory text at Sec. 725.239 regarding use of 
antibiotic resistance markers in those microorganisms. The general 
discussion of antibiotic resistance markers can be found in the 
Response to Comments document in Unit V.E.
    EPA recognizes that many factors affect the health and safety 
evaluation of use of antibiotic resistance markers. The use of 
antibiotic resistance markers is a complicated issue which has 
ramifications for products beyond the scope of TSCA. Because of the 
complexity, EPA will not issue a general policy on the use of 
antibiotic resistance markers, but will continue to evaluate their use 
in specific microorganisms on a case-by-case basis as submissions are 
received. EPA plans to pursue this issue in consultation with other 
Federal agencies who have an interest in this issue.
    5. State coordination. The proposed rule discussed EPA's procedures 
under the 1986 Policy Statement for coordinating reviews and sharing 
scientific information with appropriate State and local authorities (59 
FR 45531). EPA proposed to require persons preparing TERA submissions 
for R&D activities involving release to the environment to provide 
evidence of having notified appropriate State authorities. This issue 
is discussed in the Response to Comments document in Unit V.F.
    Although one commenter supported EPA's proposed requirement for 
State coordination, several commenters opposed the requirement. EPA has 
developed comprehensive procedures to coordinate reviews of submissions 
and to share scientific information with appropriate State and local 
authorities to the fullest extent possible without violating TSCA CBI 
requirements. Comments and concerns raised by the State(s) are given 
careful attention during the review process. State personnel receive a 
copy of any document which addresses the conditions under which the R&D 
activity, generally a field test, can be performed.
    EPA's coordination procedures would make researcher notification 
redundant. Consequently, EPA has revised Secs. 725.238(b)(3)(ii) and 
725.255(e)(1)(vi) to remove the requirement that submitters include 
evidence that State authorities have been notified in the TERA 
exemption certification and TERA submission, respectively. EPA will 
continue to encourage submitters to advise State and local authorities 
of their field test plans, although this will not be a requirement. In 
cases where submitters have informed State and local authorities of 
their test plans, EPA believes that it is appropriate to require that 
submitters inform EPA of this notification as part of their 
submissions.

VI. Economic Analysis

A. Introduction

    EPA has prepared a Regulatory Impact Analysis (RIA) assessing the 
costs, benefits, and associated impacts of regulating new 
microorganisms under TSCA as set forth in this final rule. A summary of 
key findings and estimates is presented below.

B. Regulated Community

    Although unable to quantify the exact magnitude of activity in 
biotechnology sectors affected by this rulemaking, the Agency believes 
that activities involving microorganisms falling within the scope of 
the final rule comprise a modest share of overall activity. EPA 
estimates that approximately 130 firms may be involved in commercial 
R&D or in general commercial use of potentially regulated 
microorganisms. In terms of revenue, the potentially affected universe 
appears to be divided sharply between large and small firms. EPA 
estimates roughly one-half of the companies potentially affected to 
have annual sales of $40 million or more, while most of those remaining 
are estimated to have sales under $10 million. For many of these firms, 
however, revenue generated from activities subject to this rule is 
believed to represent only a small portion of reported sales. At 
proposal, EPA also estimated that approximately 300 universities could 
be affected by the rulemaking. However, in the final rule, because of 
its implementation of a definition of commercial purposes at R&D based 
on financial indicia, EPA believes substantially fewer universities 
will be affected.

C. Costs to Submitters

    Due to data limitations and the uncertainties associated with 
projecting future product development activities in biotechnology 
application areas subject to the final rule, EPA's estimates of the 
costs of compliance associated with this rulemaking action have been 
only partially quantified. In cases where the Agency was able to 
generate quantified estimates of compliance costs, information which 
would have permitted the development of more accurate estimates was 
frequently unavailable; in such cases, the best available information 
was used, and the estimates are believed to represent a reasonable 
approximation of actual costs attributable to the rule. A summary of 
EPA's quantitative cost estimates follows.
    In assessing the potential cost impact of the final rule, EPA 
focussed on two impact years, ``Year 1'' and ``Year 5.'' Year 1 costs 
are based on the expected costs associated with biotechnology products 
in the early stage of regulation, while year 5 costs are based on a 
projection of conditions following some

[[Page 17929]]

industry growth, subsequent to rule promulgation. This approach was 
used because of the relative immaturity of the biotechnology sectors 
potentially subject to the rule, and the difficulty in attempting to 
forecast long-term technological and marketing developments. It is 
emphasized, however, that estimated costs could be significantly higher 
in the long-term, owing to continued industry expansion.
    Four major cost areas were identified, based on an analysis of the 
requirements of the rule. These areas were: costs incurred in preparing 
various types of notification submissions or documentation; costs 
incurred in complying with any post review requirements for monitoring 
or controls that may be imposed by EPA as a result of risk concerns and 
uncertainties; costs incurred in substantiating CBI claims; and one-
time costs attributable to rule familiarization.
    Incremental costs to industry (industry-wide costs net requirements 
under current policy), estimated based on prevailing wage rates for 
1987, were estimated to fall between $890,000 to $2.2 million in year 1 
and between $70,000 to $510,000 in year 5. (Year 5 costs account for 
rule familiarization only in the case of new firms entering the 
affected market areas, and therefore are much less than year 1 costs, 
where rule familiarization costs were summed over all affected 
entities.) Adjusted to reflect current rates (1995 dollars), estimated 
incremental costs range from $1.2 million to $3.0 million in year 1 and 
from $95,000 to $690,000 in year 5.
    Cost impacts on individual products will vary, depending on 
application area. Submitters qualifying for full or partial exemptions 
in connection with microorganisms intended for general commercial use 
will realize net savings relative to current reporting requirements, 
while submitters filing in connection with field experiments may 
realize an increase in regulatory burden under the rule.

D. Costs to the Federal Government

    EPA estimated the potential costs to government associated with the 
final rule. These costs arise in connection with the Agency's 
processing of individual notification submissions.
    In estimating government cost impacts, EPA included costs estimated 
to be incurred in reviewing each submittal. EPA professionals and 
members of the Biotechnology Science Advisory Committee were assumed to 
be involved in such review. In the event that post-review restrictions 
are placed on a specific activity, such as monitoring during a field 
test, additional costs attributable to the drawing up of regulatory 
documentation would be incurred.
    Incremental costs to the government were estimated, using 1987 as 
the base year for valuing compensation, to fall between $115,000 to 
$122,000 in year 1, while year 5 costs were estimated to fall between -
$105,000 (a net savings) to $4,000. Using 1995 as base year for 
compensation, estimated incremental costs range from $156,000 to 
$165,000 in year 1 and from -$143,000 to $5,300 in year 5. Savings 
arise in connection with the substantial number of full reviews that 
will be avoided due to the exemption provisions of the rule.

E. Benefits of the Rule

    EPA's regulation of new microorganisms under TSCA provides benefits 
to society through reduction of the potential for adverse impacts on 
health and the environment resulting from the use of such organisms. 
This benefit is achieved by screening new microorganisms and, when 
appropriate, imposing controls on microorganism use to protect society 
from costly and possibly irreversible damages.
    For microorganisms in general commercial use, risk reduction 
attributable strictly to the notification requirements of the final 
rule would be marginal, as these requirements are based on current 
policy. However, the rule enhances and contributes to the overall risk 
reduction potential of the Agency's program under TSCA by providing for 
a more efficient regulatory strategy relative to current policy, 
focussing society's resources on those new microorganisms of greatest 
concern.
    For microorganisms in commercial R&D, a greater proportion of 
overall risk reduction can be attributed to the rule, since reporting 
in connection with field experiments has been voluntary since 1986. 
Though the Agency has received voluntary submittals, it is uncertain 
whether this practice is universal, or whether those filing voluntarily 
would continue to do so in the absence of these rules.
    Over the long-term, regulation is also likely to encourage 
development of additional information concerning fate and effects of 
new microorganisms, to encourage the development of microorganisms 
which pose low concern for effects on human health and the environment, 
and to encourage public input into decisions concerning the use of new 
microorganisms.
    Benefits may also be realized through the rule's potential impact 
on the pace of product development. A less uncertain regulatory climate 
could stimulate business activity, as could a more reassured public. 
The rule may also reduce the possibility of continued regulatory 
activity at the State and local level. A national system of potentially 
uncoordinated rulemaking initiatives could lead to market distortion 
and hamper competitiveness.

F. Effects of the Rule on Innovative Activity

    As a result of this final rule, members of the regulated community 
may find product development strategies in connection with certain 
products to require reassessment. Since impacts of this nature could 
influence the degree of emphasis a firm places on innovative activity, 
the potential for innovation impacts was investigated.
    Though great uncertainty regarding regulatory costs and the 
potential for a particular product's commercial success make it 
impossible to estimate innovation impacts quantitatively, the effects 
of added regulatory costs and delays on a product's lifetime cash-flow 
was examined. More specifically, a number of plausible product 
development scenarios were modeled incorporating assumptions regarding 
expenditures and returns over the course of a product's useful life 
(from research to obsolescence). Regulatory burdens were then factored 
into the models, and profit impacts observed.
    Impacts realized when total regulatory costs were assumed to reach 
the upper-bound of EPA's estimated range could result in severe profit 
reductions in some cases; however, in general, EPA's analysis indicated 
that impacts should not be prohibitive, particularly when incremental 
costs are considered. Factors such as length of delay related to 
regulatory review, return rate, and obsolescence rate all play 
important roles in determining the impact of EPA's program on 
innovative activity, and these factors are expected to be highly 
variable and product-specific.

G. Impacts on Small Business

    EPA survey data suggest 42 percent of companies potentially 
affected by the rule may be small businesses. Though data were not 
available allowing the Agency to employ standard criteria for assessing 
the magnitude of small business impacts, the finding of a substantial 
portion of the regulated community to be small businesses prompted EPA 
to propose options to provide relief to such businesses. The options 
considered included reducing CBI substantiation requirements and the 
elimination of the $100 filing fee.
    Comments were submitted indicating concern for the rules impacts on

[[Page 17930]]

products of low-value or limited use, and for cost impacts on small 
companies. Comments were also received on the Agency's proposed 
alternatives for substantiation of CBI claims in connection with TERA 
submissions.
    With regard to comments regarding smaller-scale product development 
and cost impacts on small business, EPA finds that, because smaller 
scale projects would most likely be exempt or involve a relatively 
limited set of use and exposure scenarios, burdens due to regulatory 
review would be expected to be minimal; thus, the impacts of greatest 
concern to smaller institutions or organizations could be frequently 
mitigated. In considering comments regarding CBI substantiation, EPA 
has decided not to require upfront CBI substantiation in connection 
with TERA submissions, as most commenters generally indicated upfront 
substantiation to be overly burdensome for R&D. Since the Agency 
considered reducing up-front CBI substantiation requirements for small 
businesses submitting TERAs in its IRFA, EPA views the CBI 
substantiation requirements contained in the final rule as providing 
important burden relief to small businesses (or any business) 
conducting R&D.

VII. Public Record

    EPA has established a public record for this rulemaking (docket 
control number OPPTS-00049C). The record includes all information 
considered by EPA in developing this final rule. This includes all 
information in the docket, as well as information referenced in 
documents in the docket. A public version of the record without any 
confidential information is available in the TSCA Public Docket Office 
from noon to 4 p.m., Monday through Friday, except legal holidays. The 
TSCA Public Docket Office is located in Rm. NE-G607, Northeast Mall, 
401 M St., SW., Washington, DC.
    EPA has also made this final rule and certain support documents 
available electronically. They may be accessed through the Internet at: 
gopher.epa.gov or the Office of Pollution Prevention and Toxics 
Biotechnology home page at http://www.epa.gov/opptintr/biotech/.
    The record now includes the following items:
    1. All prior Federal Register Notices, and supporting public 
dockets, relating to the regulation of microbial products of 
biotechnology under TSCA. These include:
    a. The 1984 Proposed Policy Statement (49 FR 50856, December 31, 
1984).
    b. The 1986 Policy Statement (51 FR 23302, June 26, 1986).
    c. ``Biotechnology; Request for Comment on Regulatory Approach,'' 
54 FR 7027, February 15, 1989).
    2. Public comments submitted in response to each of the above 
Notices, including the comments received at the September 1989 Meeting 
which was held to discuss TSCA regulatory options for oversight of R&D.
    3. ``Principles for Federal Oversight of Biotechnology: Planned 
Introduction Into the Environment of Organisms With Modified Hereditary 
Traits,'' Office of Science and Technology Policy, 55 FR 31118, July 
31, 1990.
    4. Reports of all BSAC meetings pertaining to the development of 
this final rule.
    5. The Regulatory Impact Analysis for this final rule.
    6. Support documents and reports.
    7. Records of all communications between EPA personnel and persons 
outside EPA pertaining to the development of this final rule. (This 
does not include any inter- or intra-agency memoranda, unless 
specifically noted in the Index of this docket.)
    8. The docket also includes published literature that is cited in 
this document.
    9. The Response to Comments document responding to the public 
comments received on the September 1994 proposed rule, and all 
references cited therein.

VIII. References

    The following books, articles, and reports were used in preparing 
this final rule and were cited in this notice by the number indicated 
below:
    1. Priest, F. G., M. Goodfellow, L.A. Shute, R.C.W. Berkeley. 1987. 
``Bacillus amyloliquefaciens. sp. nov., nom.rev.'' Internat. J. Syst. 
Bacteriol. 37:69-71.
    2. U.S. Department of Health Human Services, National Institutes of 
Health (NIH). 1994. ``Guidelines for Research Involving Recombinant DNA 
Molecules (NIH Guidelines)'' (59 FR 34496, July 5, 1994).
    3. OECD. 1988. ``Recombinant DNA Safety Considerations.'' OECD, 
Paris.
    4. Radian Corporation. 1996. ``Review of past premanufacture 
notices for potential containment criteria for the 5(h)(4) exemptions 
in the proposed biotechnology rule.'' U.S. Environmental Protection 
Agency, Office of Pollution Prevention and Toxics, Chemical Engineering 
Branch, unpublished. Washington, D.C.
    5. Atlas, R. and Bartha. R. 1987. ``Microbial Ecology.'' Chapter 2 
``Survey of Microorganisms,'' pg. 19-60. Benjamin/Cummings Publishing 
Company, Inc. Menlo Park, CA.
    6. Battelle. 1988. ``Final Report on Biosafety in Large-Scale rDNA 
Processing Facilities.'' 4 volume set. U.S. EPA, Risk Reduction 
Engineering Laboratory, Cincinnati, OH.

IX. Regulatory Assessment Requirements

A. Executive Order 12866

    Under Executive Order 12866 (58 FR 51735, October 4, 1993), it has 
been determined that this rule is ``significant'' because it may raise 
novel policy issues arising out of legal mandates. As such, this action 
was submitted to OMB for review, and any comments or changes made in 
response to OMB suggestions or recommendations have been documented in 
the public record.

B. Regulatory Flexibility Act

    Pursuant to section 605(b) of the Regulatory Flexibility Act (RFA) 
(5 U.S.C. 601 et seq), the Agency hereby certifies that this final rule 
will not have a significant adverse economic impact on a substantial 
number of small entities. The factual basis for this determination is 
contained in the small business regulatory flexibility analysis, which 
is included as part of the RIA accompanying this final rule, and is 
summarized in Unit V. of this preamble. In sum, EPA believes that the 
mechanisms outlined in the final rule will minimize economic impacts on 
small businesses as much as possible, and has determined that the rule 
should not unduly burden small entities, nor hinder the industry as a 
whole from pursuing a full range of product applications.
    Information relating to this determination has been included in the 
docket for this rule, and will be provided to the Chief Counsel for 
Advocacy of the Small Business Administration upon request.

C. Paperwork Reduction Act

    The Office of Management and Budget (OMB) has approved the 
information collection requirements contained in this rule under the 
provisions of the Paperwork Reduction Act, 44 U.S.C. 3501 et seq. and 
has assigned OMB control number 2070-0012 (EPA ICR No. 574).
    This request is for an amendment to an existing ICR covering EPA's 
Premanufacture Notice (PMN) review program as is necessary to: (1) 
Collect information on new microorganisms manufactured or imported for 
commercial use, and certain new microorganisms used for research and 
development (R&D); (2) reduce reporting

[[Page 17931]]

requirements for certain categories of new microorganisms; and (3) 
require recordkeeping demonstrating compliance with conditions of 
certain exemptions for new microorganisms.
    Section 5 of TSCA gives EPA authority to review chemical substances 
prior to their manufacture, importation, or processing in the U.S. in 
order to determine whether such substances may present an unreasonable 
risk of injury to health or the environment. As explained in the 
preamble to the proposed rule and affirmed in Unit IV. earlier in this 
preamble, the Agency has determined such chemical substances to include 
microorganisms. To make a reasoned evaluation of the risk associated 
with new microorganisms, EPA needs data on each microorganism's genetic 
make-up; physical, chemical, genetic or phenotypic properties; 
manufacturing process; worker exposure; environmental release; 
production volume; potential industrial, commercial, and consumer use; 
and related test data. The submission of such data is mandatory, 
pursuant to section 5(a)(1) of TSCA, 15 U.S.C. 2604, and is to be 
submitted 90 days before manufacture or import begins. The 
confidentiality of collected information will be maintained pursuant to 
the provisions of TSCA, 15 U.S.C. 2613.
    The projected annual incremental cost to private parties associated 
with the rule is $1.2 million, with an associated burden of 41,000 
hours. Annual incremental costs may be broken down into two components 
- initialization or start-up costs (rule familiarization), estimated to 
be $575,000, and costs for information disclosure and maintenance of 
records, estimated to be $600,000. Annual burden is estimated to be 
distributed among 218 responses, averaging 188 hours per response. The 
number of potential respondents is estimated to be about 400 (not every 
possible respondent is expected to file each year).
    Burden means the total time, effort, or financial resources 
expended by persons to generate, maintain, retain, or disclose or 
provide information to or for a Federal agency. This includes the time 
needed to review instructions; develop, acquire, install, and utilize 
technology and systems for the purposes of collecting, validating, and 
verifying information, processing and maintaining information, and 
disclosing and providing information; adjust the existing ways to 
comply with any previously applicable instructions and requirements; 
train personnel to be able to respond to a collection of information; 
search data sources; complete and review the collection of information; 
and transmit or otherwise disclose the information.
    An Agency may not conduct or sponsor, and a person is not required 
to respond to a collection of information unless it displays a 
currently valid OMB control number.

D. Unfunded Mandates Reform Act and Executive Order 12875

    Pursuant to Title II of the Unfunded Mandates Reform Act of 1995 
(UMRA) (Pub. L. 104-4), EPA has determined that this action does not 
contain a Federal mandate that may result in expenditures of $100 
million or more for State, local, and tribal governments, in the 
aggregate, or the private sector in any 1 year. The costs associated 
with this action which are described in the Executive Order 12866 
section above are well below $100 million for the private sector. This 
rule does not impose any duties upon States and local government. 
Therefore, this action is not subject to the requirements of sections 
202 and 205 of the UMRA.

E. Executive Order 12898

    Pursuant to Executive Order 12898 (59 FR 7629, February 16, 1994), 
entitled Federal Actions to Address Environmental Justice in Minority 
Populations and Low-Income Populations, the Agency has considered 
environmental justice related issues with regard to the potential 
impacts of this action on the environmental and health conditions in 
low-income and minority communities. The Agency has determined that 
nothing in these notification procedures shall contribute to 
disproportionately high and adverse human health or environmental 
effects on such communities. This final rule describes informational 
requirements prior to manufacture, process, or import of new 
microorganisms based only on such microorganisms' genetic 
characteristics and, as such, shall not have the effect of excluding 
populations from participation in, denying populations the benefits of, 
or subjecting populations to discrimination because of their race, 
color, or national origin.

F. Submission to Congress and the General Accounting Office

    Under 5 U.S.C. 801(a)(1)(A) of the Administrative Procedure Act 
(APA) as amended by the Small Business Regulatory Enforcement Fairness 
Act of 1996 (Title II of Pub. L. 104-121, 110 Stat. 847), EPA submitted 
a report containing this rule and other required information to the 
U.S. Senate, the U.S. House of Representatives and the Comptroller 
General of the General Accounting Office prior to publication of the 
rule in today's Federal Register. This rule is not a ``major rule'' as 
defined by 5 U.S.C. 804(2) of the APA as amended.

List of Subjects in 40 CFR Parts 700, 720, 721, 723, and 725

    Environmental protection, Administrative practice and procedure, 
Biotechnology, Chemicals, Hazardous substances, Imports, Labeling, 
Microorganisms, Occupational safety and health, Reporting and 
recordkeeping requirements, Significant new use rule.

    Dated: March 26, 1997.
Carol M. Browner,
Administrator.
    Therefore, 40 CFR Chapter I is amended as follows:

PART 700--[AMENDED]

    1. In part 700:
    a. The authority citation for part 700 continues to read as 
follows:

    Authority: 15 U.S.C. 2625.

    b. In Sec. 700.43, by revising the introductory text and the 
definition of ``Section 5 notice'' and adding two definitions to read 
as follows:


Sec. 700.43   Definitions.

    Definitions in section 3 of the Act (15 U.S.C. 2602), as well as 
definitions contained in Secs. 704.3, 720.3, and 725.3 of this chapter, 
apply to this subpart unless otherwise specified in this section. In 
addition, the following definitions apply:
    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.
     *  *  *  *  *
    Microbial commercial activity notice or MCAN means any notice for 
microorganisms submitted to EPA pursuant to section 5(a)(1) of the Act 
in accordance with subpart D of part 725 of this chapter.
     *  *  *  *  *
    Section 5 notice means any PMN, consolidated PMN, intermediate PMN, 
significant new use notice, exemption notice, exemption application, 
any MCAN or consolidated MCAN submitted under section 5 of the Act.
     *  *  *  *  *
    c. In Sec. 700.45 by adding paragraphs (b)(2)(vi), (e)(4)(iv), 
(e)(5)(iv), (f)(4), and revising paragraphs (c) and (f)(3) to read as 
follows:

[[Page 17932]]

Sec. 700.45  Fee payments.

    *  *  *  *  *
    (b) *  *  *
    (2) *  *  *
    (vi) MCAN and consolidated MCAN. Persons shall remit a fee of 
$2,500 for each MCAN or consolidated MCAN submitted.
    (c) No fee required. Persons are exempt from remitting any fee for 
submissions under Secs. 720.38, 723.50, and subparts E, F, and G of 
part 725 of this chapter.
     *  *  *  *  *  
    (e) *  *  *
    (4) *  *  *
    (iv) Each person who remits the fee identified in paragraph (b)(1) 
of this section for a MCAN for a microorganism shall include the words, 
``The company identified in this notice is a small business concern 
under 40 CFR 700.43 and has remitted a fee of $100 in accordance with 
40 CFR 700.45(d),'' in the certification required in Sec. 725.25(b) of 
this chapter.
    (5) *  *  *
    (iv) Each person who remits a fee identified in paragraph (b)(2) of 
this section for a MCAN for a microorganism shall include the words, 
``The company identified in this notice has remitted the fee specified 
in 40 CFR 700.45(b),'' in the certification required in Sec. 725.25(b) 
of this chapter.
    (f) *  *  *
    (3) The notice is incomplete under either Sec. 720.65(c) or 725.33, 
of this chapter.
    (4) That as of the date of submission of the notice: the 
microorganism that is the subject of a MCAN is not a new microorganism; 
nor is the use involving the microorganism a significant new use.
    d. By revising Sec. 700.49 to read as follows:


Sec. 700.49   Failure to remit fees.

    EPA will not consider a section 5 notice to be complete unless the 
appropriate certification under Sec. 700.45(e) is included and until 
the appropriate remittance under Sec. 700.45(b) has been sent to EPA as 
provided in Sec. 700.45(e) and received by EPA. EPA will notify the 
submitter that the section 5 notice is incomplete in accordance with 
Secs. 720.65(c) and 725.33 of this chapter.

PART 720--[AMENDED]

    2. In part 720:
    a. The authority citation for part 720 continues to read as 
follows:

    Authority: 15 U.S.C. 2604, 2607, and 2613.

    b. In Sec. 720.1, by revising the first sentence and adding a 
sentence to read as follows:


Sec. 720.1   Scope.

    This part establishes procedures for the reporting of new chemical 
substances by manufacturers and importers under section 5 of the Toxic 
Substances Control Act, 15 U.S.C. 2604. This part applies to 
microorganisms only to the extent provided by part 725 of this chapter. 
*  *  *  

PART 721--[AMENDED]

    3. In part 721:
    a. The authority citation for part 721 continues to read as 
follows:

    Authority: 15 U.S.C. 2604, 2607, and 2625(c).

    b. In Sec. 721.1(a), by revising the first sentence to read as 
follows:


Sec. 721.1   Scope and applicability.

    This part identifies uses of chemical substances, except for 
microorganisms regulated under part 725 of this chapter, which EPA has 
determined are significant new uses under the authority of section 
5(a)(2) of the Toxic Substances Control Act. *  *  *  

PART 723--[AMENDED]

    4. In part 723:
    a. The authority citation for part 723 continues to read as 
follows:

    Authority: 15 U.S.C. 2604.

    b. In Sec. 723.50, by revising the section heading and adding 
paragraph (a)(3) to read as follows:


Sec. 723.50   Chemical substances manufactured in quantities of 10,000 
kilograms or less per year, and chemical substances with low 
environmental releases and human exposures.

    (a) *  *  *
    (3) This section does not apply to microorganisms subject to part 
725 of this chapter.
    *  *  *  *  *  
    c. In Sec. 723.175, by revising paragraph (a)(1) to read as 
follows:


Sec. 723.175   Chemical substances used in or for the manufacture or 
processing of instant photographic and peel-apart film articles.

    (a) Purpose and scope. (1) This section grants an exemption from 
the premanufacture notice requirements of section 5(a)(1)(A) of the 
Toxic Substances Control Act (15 U.S.C. 2604(a)(1)(A)) for the 
manufacture and processing of new chemical substances used in or for 
the manufacture or processing of instant photographic and peel-apart 
film articles. This section does not apply to microorganisms subject to 
part 725 of this chapter.
    *  *  *  *  *  
    d. In Sec. 723.250, by revising paragraph (a)(1) to read as 
follows:


Sec. 723.250   Polymers.

    (a) Purpose and scope. (1) This section grants an exemption from 
certain of the premanufacture notice requirements of section 5(a)(1)(A) 
of the Toxic Substances Control Act (15 U.S.C. 2604(a)(1)(A)) for the 
manufacture of certain polymers. This section does not apply to 
microorganisms subject to part 725 of this chapter.
    *  *  *  *  *  
    5. Part 725 is added to read as follows:

PART 725--REPORTING REQUIREMENTS AND REVIEW PROCESSES FOR 
MICROORGANISMS

Subpart A--General Provisions and Applicability
Sec.
725.1    Scope and purpose.
725.3    Definitions.
725.8    Coverage of this part.
725.12   Identification of microorganisms for Inventory and other 
listing purposes.
725.15   Determining applicability when microorganism identity or 
use is confidential or uncertain.
725.17   Consultation with EPA.
Subpart B--Administrative Procedures
725.20   Scope and purpose.
725.25   General administrative requirements.
725.27   Submissions.
725.28   Notice that submission is not required.
725.29   EPA acknowledgement of receipt of submission.
725.32   Errors in the submission.
725.33   Incomplete submissions.
725.36   New information.
725.40   Notice in the Federal Register.
725.50   EPA review.
725.54   Suspension of the review period.
725.56   Extension of the review period.
725.60   Withdrawal of submission by the submitter.
725.65   Recordkeeping.
725.67   Applications to exempt new microorganisms from this part.
725.70   Compliance.
725.75   Inspections.
Subpart C--Confidentiality and Public Access to Information
725.80   General provisions for confidentiality claims.
725.85   Microorganism identity.
725.88   Uses of a microorganism.
725.92   Data from health and safety studies of microorganisms.
725.94   Substantiation requirements.
725.95   Public file.
Subpart D--Microbial Commercial Activities Notification Requirements
725.100   Scope and purpose.
725.105   Persons who must report.
725.110   Persons not subject to this subpart.
725.150   Procedural requirements for this subpart.
725.155   Information to be included in the MCAN.

[[Page 17933]]

725.160   Submission of health and environmental effects data.
725.170   EPA review of the MCAN.
725.190   Notice of commencement of manufacture or import.
Subpart E--Exemptions for Research and Development Activities
725.200   Scope and purpose.
725.205   Persons who may report under this subpart.
725.232   Activities subject to the jurisdiction of other Federal 
programs or agencies.
725.234   Activities conducted inside a structure.
725.235   Conditions of exemption for activities conducted inside a 
structure.
725.238   Activities conducted outside a structure.
725.239   Use of specific microorganisms in activities conducted 
outside a structure.
725.250   Procedural requirements for the TERA.
725.255   Information to be included in the TERA.
725.260   Submission of health and environmental effects data.
725.270   EPA review of the TERA.
725.288   Revocation or modification of TERA approval.
Subpart F--Exemptions for Test Marketing
725.300   Scope and purpose.
725.305   Persons who may apply under this subpart.
725.350   Procedural requirements for this subpart.
725.355   Information to be included in the TME application.
725.370   EPA review of the TME application.
Subpart G--General Exemptions for New Microorganisms
725.400   Scope and purpose.
725.420   Recipient microorganisms.
725.421   Introduced genetic material.
725.422   Physical containment and control technologies.
725.424   Requirements for the Tier I exemption.
725.426   Applicability of the Tier I exemption.
725.428   Requirements for the Tier II exemption.
725.450   Procedural requirements for the Tier II exemption.
725.455   Information to be included in the Tier II exemption 
request.
725.470   EPA review of the Tier II exemption request.
Subparts H--K [Reserved]
Subpart L--Additional Procedures for Reporting on Significant New Uses 
of Microorganisms
725.900   Scope and purpose.
725.910   Persons excluded from reporting significant new uses.
725.912   Exemptions.
725.920   Exports and imports.
725.950   Additional recordkeeping requirements.
725.975   EPA approval of alternative control measures.
725.980   Expedited procedures for issuing significant new use rules 
for microorganisms subject to section 5(e) orders.
725.984   Modification or revocation of certain notification 
requirements.
Subpart M--Significant New Uses for Specific Microorganisms
725.1000   Scope.

    Authority: 15 U.S.C. 2604, 2607, 2613, and 2625.

Subpart A--General Provisions and Applicability


Sec. 725.1  Scope and purpose.

    (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 Sec. 725.100 for new microorganisms and 
Sec. 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 Secs. 725.424 and 725.428), test marketing 
activities (see Sec. 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 
Sec. 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 Sec. 725.232), certain kinds of contained R&D activities 
(see Sec. 725.234), and R&D activities using certain listed 
microorganisms (see Sec. 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.


Sec. 725.3   Definitions.

    Definitions in section 3 of the Act (15 U.S.C. 2602), as well as 
definitions contained in Secs. 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.

[[Page 17934]]

    (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 
Sec. 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.
    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 Sec. 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:

[[Page 17935]]

    (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.


Sec. 725.8   Coverage of this part.

    (a) Microorganisms subject to this part. Only microorganisms which 
are manufactured, imported, or processed for commercial purposes, as 
defined in Sec. 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 Sec. 720.3(e) of 
this chapter.
    (2) Any microbial mixture as defined in Sec. 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 Sec. 721.3 of this chapter.


Sec. 725.12   Identification of microorganisms for Inventory and other 
listing purposes.

    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.


Sec. 725.15   Determining applicability when microorganism identity or 
use is confidential or uncertain.

    (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 Sec. 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 
Sec. 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 Sec. 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, import, or process are equivalent to 
specific microorganisms described on the Inventory, in Sec. 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, import, or 
process a microorganism, the person who intends to manufacture, import, 
or process the microorganism must submit the following information in 
writing to the Office of Pollution Prevention and Toxics, Document 
Control Officer, 7407, 401 M St., SW., Washington, DC 20460, ATTN: 
BIOTECH bona fide submission.
    (i) Taxonomic designations and supplemental information required by 
Sec. 725.12.
    (ii) A signed statement certifying that the submitter intends to 
manufacture, 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

[[Page 17936]]

manufacture, 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, 
importer, or processor under this paragraph to determine whether that 
person has shown a bona fide intent to manufacture, import, or process 
the microorganism. If necessary, EPA will compare this information to 
the information requested for the confidential microorganism under 
Sec. 725.85(b)(3)(iii).
    (e) In order for EPA to make a conclusive determination of the 
microorganism's status, the proposed manufacturer, importer, or 
processor must show a bona fide intent to manufacture, 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, 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 Sec. 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, import, 
or process the microorganism and therefore was told that the 
microorganism is on the Inventory, in Sec. 725.239, or in subpart M of 
this part.
    (g) A disclosure to a person with a bona fide intent to 
manufacture, import, or process a particular microorganism that the 
microorganism is on the Inventory, in Sec. 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.


Sec. 725.17  Consultation with EPA.

    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, 401 M St., 
SW., 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: TSCA-
H[email protected].
Subpart B--Administrative Procedures


Sec. 725.20   Scope and purpose.

    This subpart describes general administrative procedures applicable 
to all persons who submit MCANs and exemption requests to EPA under 
section 5 of the Act for microorganisms.


Sec. 725.25   General administrative requirements.

    (a) General. (1) Each person who is subject to the notification 
provisions of this part must complete, sign, and submit a MCAN or 
exemption request containing the information as required for the 
appropriate submission under this part. Except as otherwise provided, 
each submission must include all referenced attachments. All 
information in the submission (unless certain attachments appear in the 
open scientific literature) must be in English. All information 
submitted must be true and correct.
    (2) In addition to specific information required, the submitter 
should submit all information known to or reasonably ascertainable by 
the submitter that would permit EPA to make a reasoned evaluation of 
the human health and environmental effects of the microorganism and any 
microbial mixture or article that may contain the microorganism.
    (b) Certification. Persons submitting MCANs and exemption requests 
to EPA under this part, and material related to their reporting 
obligations under this part, must attach the following statement to any 
information submitted to EPA. This statement must be signed and dated 
by an authorized official of the submitter:

    I certify that to the best of my knowledge and belief: The 
company named in this submission intends to manufacture, import, or 
process for a commercial purpose, other than in small quantities 
solely for research and development, the microorganism identified in 
this submission. All information provided in this submission is 
complete and truthful as of the date of submission. I am including 
with this submission all test data in my possession or control and a 
description of all other data known to or reasonably ascertainable 
by me as required by 40 CFR 725.160 or 725.260.

    (c) Where to submit information under this part. Persons submitting 
MCANs and exemption requests to EPA under this part, and material 
related to their reporting obligations under this part, must send them 
to: TSCA Document Processing Center (7407), Rm. L-100, Office of 
Pollution Prevention and Toxics, U.S. Environmental Protection Agency, 
401 M St., SW., Washington, DC 20460.
    (d) General requirements for submission of data. (1) Submissions 
under this part must include the information described in Sec. 725.155, 
725.255, 725.355, or 725.455, as appropriate, to the extent such 
information is known to or reasonably ascertainable by the submitter.
    (2) In accordance with Sec. 725.160 or 725.260, as appropriate, the 
submission must also include any test data in the submitter's 
possession or control and descriptions of other data which are known to 
or reasonably ascertainable by the submitter and which concern the 
health and environmental effects of the microorganism.
    (e) Agency or joint submissions. (1) A manufacturer or importer may 
designate an agent to submit the MCAN or exemption request. Both the 
manufacturer or importer and the agent must sign the certification 
required in paragraph (b) of this section.
    (2) A manufacturer or importer may authorize another person (e.g., 
a foreign manufacturer or supplier, or a toll manufacturer) to report 
some of the information required in the MCAN or exemption request to 
EPA on its behalf. If separate portions of a joint submission are not 
submitted together, the submitter must indicate which information will 
be supplied by another person and identify that person. The 
manufacturer or importer and any other person supplying the information 
must sign the certification required by paragraph (b) of this section.
    (3) If EPA receives a submission which does not include the 
information required, which the submitter indicates that it has 
authorized another person to provide, the review period will not begin 
until EPA receives all of the required information.
    (f) Microorganisms subject to a section 4 test rule. (1) Except as 
provided in paragraph (f)(3) of this section, if a

[[Page 17937]]

person intends to manufacture or import a new microorganism which is 
subject to the notification requirements of this part, and the 
microorganism is subject to a test rule promulgated under section 4 of 
the Act before the notice is submitted, section 5(b)(1) of the Act 
requires the person to submit the test data required by the testing 
rule with the notice. The person must submit the data in the form and 
manner specified in the test rule and in accordance with Sec. 725.160. 
If the person does not submit the test data, the submission is 
incomplete and EPA will follow the procedures in Sec. 725.33.
    (2) If EPA has granted the submitter an exemption under section 
4(c) of the Act from the requirement to conduct tests and submit data, 
the person may not file a MCAN or TERA until EPA receives the test 
data.
    (3) If EPA has granted the submitter an exemption under section 
4(c) of the Act and if another person previously has submitted the test 
data to EPA, the exempted person may either submit the test data or 
provide the following information as part of the notice:
    (i) The name, title, and address of the person who submitted the 
test data to EPA.
    (ii) The date the test data were submitted to EPA.
    (iii) A citation for the test rule.
    (iv) A description of the exemption and a reference identifying it.
    (g) Microorganisms subject to a section 5(b)(4) rule. (1) If a 
person:
    (i) Intends to manufacture or import a microorganism which is 
subject to the notification requirements of this part and which is 
subject to a rule issued under section 5(b)(4) of the Act; and
    (ii) Is not required by a rule issued under section 4 of the Act to 
submit test data for the microorganism before the filing of a 
submission, the person must submit to EPA data described in paragraph 
(g)(2) of this section at the time the submission is filed.
    (2) Data submitted under paragraph (g)(1) of this section must be 
data which the person submitting the notice believes show that the 
manufacture, processing, distribution in commerce, use, and disposal of 
the microorganism, or any combination of such activities, will not 
present an unreasonable risk of injury to health or the environment.
    (h) Data that need not be submitted. Specific data requirements are 
listed in subparts D, E, F, G, and L of this part. The following is a 
list of data that need not be submitted under this part:
    (1) Data previously submitted to EPA. (i) A person need not submit 
any data previously submitted to EPA with no claims of confidentiality 
if the new submission includes: the office or person to whom the data 
were submitted; the date of submission; and, if appropriate, a standard 
literature citation as specified in Sec. 725.160(a)(3)(ii).
    (ii) For data previously submitted to EPA with a claim of 
confidentiality, the person must resubmit the data with the new 
submission and any claim of confidentiality, under Sec. 725.80.
    (2) Efficacy data. This part does not require submission of any 
data related solely to product efficacy. However, including efficacy 
data will improve EPA's ability to assess the benefits of the use of 
the microorganism. This does not exempt a person from submitting any of 
the data specified in Sec. 725.160 or 725.260.
    (3) Non-U.S. exposure data. This part does not require submission 
of any data which relates only to exposure of humans or the environment 
outside the United States. This does not exclude nonexposure data such 
as data on health effects (including epidemiological studies), 
ecological effects, physical and chemical properties, or environmental 
fate characteristics.


Sec. 725.27   Submissions.

    Each person who is required to submit information under this part 
must submit the information in the form and manner set forth in the 
appropriate subpart.
    (a) Requirements specific to MCANs are described in Secs. 725.150 
through 725.160.
    (b) Requirements specific to TERAs are described in Secs. 725.250 
through 725.260.
    (c) Requirements specific to test marketing exemptions (TMEs) are 
described in Secs. 725.350 and 725.355.
    (d) Requirements specific to Tier I and Tier II exemptions for 
certain general commercial uses are described in Secs. 725.424 through 
725.470.
    (e) Additional requirements specific to significant new uses for 
microorganisms are described at Sec. 725.950.


Sec. 725.28   Notice that submission is not required.

    When EPA receives a MCAN or exemption request, EPA will review it 
to determine whether the microorganism is subject to the requirements 
of this part. If EPA determines that the microorganism is not subject 
to these requirements, EPA will notify the submitter that section 5 of 
the Act does not prevent the manufacture, import, or processing of the 
microorganism and that the submission is not needed.


Sec. 725.29   EPA acknowledgement of receipt of submission.

    (a) EPA will acknowledge receipt of each submission by sending the 
submitter a letter that identifies the number assigned to each MCAN or 
exemption request and the date on which the review period begins. The 
review period will begin on the date the MCAN or exemption request is 
received by the Office of Pollution Prevention and Toxics Document 
Control Officer.
    (b) The acknowledgement does not constitute a finding by EPA that 
the submission is in compliance with this part.


Sec. 725.32   Errors in the submission.

    (a) Within 30 days of receipt of the submission, EPA may request 
that the submitter remedy errors in the submission. The following are 
examples of such errors:
    (1) Failure to date the submission.
    (2) Typographical errors that cause data to be misleading or 
answers to any questions to be unclear.
    (3) Contradictory information.
    (4) Ambiguous statements or information.
    (b) In the request to correct the submission, EPA will explain the 
action which the submitter must take to correct the submission.
    (c) If the submitter fails to correct the submission within 15 days 
of receipt of the request, EPA may extend the review period.


Sec. 725.33   Incomplete submissions.

    (a) A submission under this part is not complete, and the review 
period does not begin, if:
    (1) The wrong person files the submission.
    (2) The submitter does not attach and sign the certification 
statement as required by Sec. 725.25(b).
    (3) Some or all of the information in the submission or any 
attachments are not in English, except for published scientific 
literature.
    (4) The submitter does not provide information that is required by 
sections 5(d)(1)(B) and (C) of the Act and Sec. 725.160 or 725.260, as 
appropriate.
    (5) The submitter does not provide information required by 
Sec. 725.25, 725.155, 725.255, 725.355, or 725.455, as appropriate, or 
indicate that it is not known to or reasonably ascertainable by the 
submitter.
    (6) The submitter has asserted confidentiality claims and has 
failed to:
    (i) Submit a second copy of the submission with all confidential 
information deleted for the public file, as required by 
Sec. 725.80(b)(2).
    (ii) Comply with the substantiation requirements as described in 
Sec. 725.94.

[[Page 17938]]

    (7) The submitter does not include any information required by 
section 5(b)(1) of the Act and pursuant to a rule promulgated under 
section 4 of the Act, as required by Sec. 725.25(f).
    (8) The submitter does not submit data which the submitter believes 
show that the microorganism will not present an unreasonable risk of 
injury to health or the environment, if EPA has listed the 
microorganism under section 5(b)(4) of the Act, as required in 
Sec. 725.25(g).
    (9) For MCANs, the submitter does not remit the fees required by 
Sec. 700.45(b)(1) or (b)(2)(vi) of this chapter.
    (b)(1) If EPA receives an incomplete submission under this part, 
the Director, or a designee, will notify the submitter within 30 days 
of receipt that the submission is incomplete and that the review period 
will not begin until EPA receives a complete submission.
    (2) If EPA obtains additional information during the review period 
for any submission that indicates the original submission was 
incomplete, the Director, or a designee, may declare the submission 
incomplete within 30 days after EPA obtains the additional information 
and so notify the submitter.
    (c) The notification that a submission is incomplete under 
paragraph (b) of this section will include:
    (1) A statement of the basis of EPA's determination that the 
submission is incomplete.
    (2) The requirements for correcting the incomplete submission.
    (3) Information on procedures under paragraph (d) of this section 
for filing objections to the determination or requesting modification 
of the requirements for completing the submission.
    (d) Within 10 days after receipt of notification by EPA that a 
submission is incomplete, the submitter may file written objections 
requesting that EPA accept the submission as complete or modify the 
requirements necessary to complete the submission.
    (e)(1) EPA will consider the objections filed by the submitter. The 
Director, or a designee, will determine whether the submission was 
complete or incomplete, or whether to modify the requirements for 
completing the submission. EPA will notify the submitter in writing of 
EPA's response within 10 days of receiving the objections.
    (2) If the Director, or a designee, determines, in response to the 
objection, that the submission was complete, the review period will be 
deemed suspended on the date EPA declared the submission incomplete, 
and will resume on the date that the submission is declared complete. 
The submitter need not correct the submission as EPA originally 
requested. If EPA can complete its review within the review period 
beginning on the date of the submission, the Director, or a designee, 
may inform the submitter that the running of the review period will 
resume on the date EPA originally declared it incomplete.
    (3) If the Director, or a designee, modifies the requirements for 
completing the submission or concurs with EPA's original determination, 
the review period will begin when EPA receives a complete submission.
    (f) If EPA discovers at any time that a person submitted materially 
false or misleading statements in information submitted under this 
part, EPA may find that the submission was incomplete from the date it 
was submitted, and take any other appropriate action.


Sec. 725.36   New information.

    (a) During the review period, if a submitter possesses, controls, 
or knows of new information that materially adds to, changes, or 
otherwise makes significantly more complete the information included in 
the MCAN or exemption request, the submitter must send that information 
to the address listed in Sec. 725.25(c) within 10 days of receiving the 
new information, but no later than 5 days before the end of the review 
period.
    (b) The new submission must clearly identify the submitter, the 
MCAN or exemption request to which the new information is related, and 
the number assigned to that submission by EPA, if known to the 
submitter.
    (c) If the new information becomes available during the last 5 days 
of the review period, the submitter must immediately inform the EPA 
contact for that submission by telephone of the new information.


Sec. 725.40   Notice in the Federal Register.

    (a) Filing of Federal Register notice. After EPA receives a MCAN or 
an exemption request under this part, EPA will issue a notice in the 
Federal Register including the information specified in paragraph (b) 
of this section.
    (b) Contents of notice. (1) In the public interest, the specific 
microorganism identity listed in the submission will be published in 
the Federal Register unless the submitter has claimed the microorganism 
identity confidential. If the submitter claims confidentiality, a 
generic name will be published in accordance with Sec. 725.85.
    (2) The categories of use of the microorganism will be published as 
reported in the submission unless this information is claimed 
confidential. If confidentiality is claimed, the generic information 
which is submitted under Sec. 725.88 will be published.
    (3) A list of information submitted in accordance with 
Sec. 725.160(a), 725.255, 725.260, 725.355, or 725.455, as appropriate, 
will be published.
    (4) The submitter's identity will be published, unless the 
submitter has claimed it confidential.
    (c) Publication of exemption decisions. Following the expiration of 
the appropriate review period for the exemption request, EPA will issue 
a notice in the Federal Register indicating whether the request has 
been approved or denied and the reasons for the decision.


Sec. 725.50   EPA review.

     (a) MCANs. The review period specified in section 5(a) of the Act 
for MCANs runs for 90 days from the date the Document Control Officer 
receives a complete submission, or the date EPA determines the 
submission is complete under Sec. 725.33, unless the Agency extends the 
review period under section 5(c) of the Act and Sec. 725.56.
    (b) Exemption requests. The review period starts on the date the 
Document Control Officer receives a complete exemption request, or the 
date EPA determines the request is complete under Sec. 725.33, unless 
the Agency extends the review period under Sec. 725.56. The review 
periods for exemption requests run as follows:
    (1) TERAs. The review period for TERAs is 60 days.
    (2) TMEs. The review period for TMEs is 45 days.
    (3) Tier II exemption requests. The review period for Tier II 
exemption requests is 45 days.


Sec. 725.54   Suspension of the review period.

    (a) A submitter may voluntarily suspend the running of the review 
period if the Director, or a designee, agrees. If the Director does not 
agree, the review period will continue to run, and EPA will notify the 
submitter. A submitter may request a suspension at any time during the 
review period. The suspension must be for a specified period of time.
    (b) A request for suspension may be made in writing to the address 
listed in Sec. 725.25(c). The suspension also may be made orally, 
including by telephone, to the submitter's EPA contact for that 
submission. EPA will send the submitter a written confirmation that the 
suspension has been granted.
    (1) An oral request may be granted for no longer than 15 days. To 
obtain a

[[Page 17939]]

longer suspension, the Document Control Officer for the Office of 
Pollution Prevention and Toxics must receive written confirmation of 
the oral request. The review period is suspended as of the date of the 
oral request.
    (2) If the submitter has not made a previous oral request, the 
running of the review period is suspended as of the date of receipt of 
the written request by the Document Control Officer for the Office of 
Pollution Prevention and Toxics.


Sec. 725.56   Extension of the review period.

    (a) At any time during the review period, EPA may unilaterally 
determine that good cause exists to extend the review period specified 
for MCANs, or the exemption requests.
    (b) If EPA makes such a determination, EPA:
    (1) Will notify the submitter that EPA is extending the review 
period for a specified length of time and state the reasons for the 
extension.
    (2) For MCANs, EPA may issue a notice for publication in the 
Federal Register which states that EPA is extending the review period 
and gives the reasons for the extension.
    (c) The total period of the extension may be for a period of up to 
the same length of time as specified for each type of submission in 
Sec. 725.50. If the initial extension is for less than the total time 
allowed, EPA may make additional extensions. However, the sum of the 
extensions may not exceed the total allowed.
    (d) The following are examples of situations in which EPA may find 
that good cause exists for extending the review period:
    (1) EPA has reviewed the submission and is seeking additional 
information.
    (2) EPA has received significant additional information during the 
review period.
    (3) The submitter has failed to correct a submission after 
receiving EPA's request under Sec. 725.32.
    (4) EPA has reviewed the submission and determined that there is a 
significant possibility that the microorganism will be regulated under 
section 5(e) or section 5(f) of the Act, but EPA is unable to initiate 
regulatory action within the initial review period.


Sec. 725.60   Withdrawal of submission by the submitter.

    (a) A submitter may withdraw a submission during the review period. 
A statement of withdrawal must be made in writing to the address listed 
in Sec. 725.25(c). The withdrawal is effective upon receipt of the 
statement by the Document Control Officer.
    (b) If a manufacturer, importer, or processor who withdrew a 
submission later resubmits a submission for the same microorganism, a 
new review period begins.


Sec. 725.65   Recordkeeping.

    (a) General provisions. (1) Any person who submits a notice under 
this part must retain documentation of information in the submission, 
including:
    (i) Any data in the submitter's possession or control; and
    (ii) Records of production volume for the first 3 years of 
manufacture, import, or processing.
    (2) Any person who submits a notice under this part must retain 
documentation of the date of commencement of testing, manufacture, 
import, or processing.
    (3) Any person who is exempt from some or all of the reporting 
requirements of this part must retain documentation that supports the 
exemption.
    (4) All information required by this section must be retained for 3 
years from the date of commencement of each activity for which records 
are required under this part.
    (b) Specific requirements. In addition to the requirements of 
paragraph (a) of this section, specific recordkeeping requirements 
included in certain subparts must also be followed.
    (1) Additional recordkeeping requirements for activities conducted 
inside a structure are set forth in Sec. 725.235(h).
    (2) Additional recordkeeping requirements for TERAs are set forth 
in Sec. 725.250(f).
    (3) Additional recordkeeping requirements for TMEs are set forth in 
Sec. 725.350(c).
    (4) Additional recordkeeping requirements for Tier I exemptions 
under subpart G of this part are set forth in Sec. 725.424(a)(5).
    (5) Additional recordkeeping requirements for Tier II exemptions 
under subpart G of this part are set forth in Sec. 725.450(d).
    (6) Additional recordkeeping requirements for significant new uses 
of microorganisms reported under subpart L of this part are set forth 
in Sec. 725.850. Recordkeeping requirements may also be included when a 
microorganism and significant new use are added to subpart M of this 
part.


Sec. 725.67   Applications to exempt new microorganisms from this part.

    (a) Submission. (1) Any manufacturer or importer of a new 
microorganism may request, under section 5(h)(4) of the Act, an 
exemption, in whole or in part, from this part by sending a Letter of 
Application to the Chief, New Chemicals Branch, Chemical Control 
Division, Office of Pollution Prevention and Toxics, U.S. Environmental 
Protection Agency, 401 M St., SW., Washington, DC 20460.
    (2) General provisions. The Letter of Application should provide 
information to show that any activities affected by the requested 
exemption will not present an unreasonable risk of injury to health or 
the environment. This information should include data described in the 
following paragraphs.
    (i) The effects of the new microorganism on health and the 
environment.
    (ii) The magnitude of exposure of human beings and the environment 
to the new microorganism.
    (iii) The benefits of the new microorganism for various uses and 
the availability of substitutes for such uses.
     (iv) The reasonably ascertainable economic consequences of 
granting or denying the exemption, including effects on the national 
economy, small business, and technological innovation.
    (3) Specific requirements. In addition to the requirements of 
paragraph (a)(2) of this section, the specific information requirements 
of the relevant subpart under which the exemption is sought should be 
met.
    (i) Exemption from MCAN reporting under subpart D. Information 
requirements are set forth in Secs. 725.155 and 725.160.
    (ii) Exemption from TERA reporting under subpart E. Information 
requirements are set forth in Secs. 725.255 and 725.260.
    (iii) Listing a recipient microorganism as eligible for exemption 
under subpart G. Information regarding the following criteria should be 
addressed in an application to list a recipient microorganism under 
Sec. 725.420:
    (A) Identification and classification of the microorganism using 
available genotypic and phenotypic information;
    (B) Information to evaluate the relationship of the microorganism 
to any other closely related microorganisms which have a potential for 
adverse effects on health or the environment;
    (C) A history of safe commercial use for the microorganism;
    (D) Commercial uses indicating that the microorganism products 
might be subject to TSCA;
    (E) Studies which indicate the potential for the microorganism to 
cause adverse effects to health or the environment; and

[[Page 17940]]

    (F) Studies which indicate the survival characteristics of the 
microorganism in the environment.
     (b) Processing of the Letter of Application by EPA--(1) Grant of 
the Application. If, after consideration of the Letter of Application 
and any other relevant information available to EPA, the Assistant 
Administrator for Prevention, Pesticides and Toxic Substances makes a 
preliminary determination that the new microorganism will not present 
an unreasonable risk of injury to health or the environment, the 
Assistant Administrator will propose a rule to grant the exemption 
using the applicable procedures in part 750 of this chapter.
    (2) Denial of the application. If the Assistant Administrator 
decides that the preliminary determination described in paragraph 
(b)(1) of this section cannot be made, the application will be denied 
by sending the applicant a written statement with the Assistant 
Administrator's reasons for denial.
    (c) Processing of the exemption--(1) Unreasonable risk standard. 
Granting a section 5(h)(4) exemption requires a determination that the 
activities will not present an unreasonable risk of injury to health or 
the environment.
    (i) An unreasonable risk determination under the Act is an 
administrative judgment that requires balancing of the harm to health 
or the environment that a chemical substance may cause and the 
magnitude and severity of that harm, against the social and economic 
effects on society of EPA action to reduce that harm.
    (ii) A determination of unreasonable risk under section 5(h)(4) of 
the Act will examine the reasonably ascertainable economic and social 
consequences of granting or denying the exemption after consideration 
of the effect on the national economy, small business, technological 
innovation, the environment, and public health.
    (2) Grant of the exemption. The exemption will be granted if the 
Assistant Administrator determines, after consideration of all relevant 
evidence presented in the rulemaking proceeding described in paragraph 
(b)(1) of this section, that the new microorganism will not present an 
unreasonable risk of injury to health or the environment.
    (3) Denial of the exemption. The exemption will be denied if the 
Assistant Administrator determines, after consideration of all relevant 
evidence presented in the rulemaking proceeding described in paragraph 
(b)(1) of this section, that the determination described in paragraph 
(c)(2) of this section cannot be made. A final decision terminating the 
rulemaking proceeding will be published in the Federal Register.


Sec. 725.70   Compliance.

    (a) Failure to comply with any provision of this part is a 
violation of section 15 of the Act (15 U.S.C. 2614).
    (b) A person who manufactures or imports a microorganism before a 
MCAN is submitted and the MCAN review period expires is in violation of 
section 15 of the Act even if that person was not required to submit 
the MCAN under Sec. 725.105.
    (c) Using a microorganism which a person knew or had reason to know 
was manufactured, processed, or distributed in commerce in violation of 
section 5 of the Act or this part is a violation of section 15 of the 
Act (15 U.S.C. 2614).
    (d) Failure or refusal to establish and maintain records or to 
permit access to or copying of records, as required by the Act, is a 
violation of section 15 of the Act (15 U.S.C. 2614).
    (e) Failure or refusal to permit entry or inspection as required by 
section 11 of the Act is a violation of section 15 of the Act (15 
U.S.C. 2614).
    (f) Violators may be subject to the civil and criminal penalties in 
section 16 of the Act (15 U.S.C. 2615) for each violation. Persons who 
submit materially misleading or false information in connection with 
the requirements of any provision of this part may be subject to 
penalties calculated as if they never filed their submissions.
    (g) EPA may seek to enjoin the manufacture or processing of a 
microorganism in violation of this part or act to seize any 
microorganism manufactured or processed in violation of this part or 
take other actions under the authority of section 7 of the Act (15 
U.S.C. 2606) or section 17 of the Act (15 U.S.C. 2616).


Sec. 725.75   Inspections.

    EPA will conduct inspections under section 11 of the Act to assure 
compliance with section 5 of the Act and this part, to verify that 
information required by EPA under this part is true and correct, and to 
audit data submitted to EPA under this part.
Subpart C--Confidentiality and Public Access to Information


Sec. 725.80  General provisions for confidentiality claims.

    (a) A person may assert a claim of confidentiality for any 
information submitted to EPA under this part. However,
    (1) Any person who asserts a claim of confidentiality for portions 
of the specific microorganism identity must provide the information as 
described in Sec. 725.85.
    (2) Any person who asserts a claim of confidentiality for a use of 
a microorganism must provide the information as described in 
Sec. 725.88.
    (3) Any person who asserts a claim of confidentiality for 
information contained in a health and safety study of a microorganism 
must provide the information described in Sec. 725.92.
    (b) Any claim of confidentiality must accompany the information 
when it is submitted to EPA.
    (1) When a person submits any information under this part, 
including any attachments, for which claims of confidentiality are 
made, the claim(s) must be asserted by circling the specific 
information which is claimed and marking the page on which that 
information appears with an appropriate designation such as ``trade 
secret,'' ``TSCA CBI,'' or ``confidential business information.''
    (2) If any information is claimed confidential, the person must 
submit two copies of the document including the claimed information.
    (i) One copy of the document must be complete. In that copy, the 
submitter must mark the information which is claimed as confidential in 
the manner prescribed in paragraph (b)(1) of this section.
    (ii) The second copy must be complete except that all information 
claimed as confidential in the first copy must be deleted. EPA will 
place the second copy in the public file.
    (iii) If the submitter does not provide the second copy, the 
submission is incomplete and the review period does not begin to run 
until EPA receives the second copy, in accordance with Sec. 725.33.
    (iv) Any information contained within the copy submitted under 
paragraph (b)(2)(ii) of this section which has been in the public file 
for more than 30 days will be presumed to be in the public domain, 
notwithstanding any assertion of confidentiality made under this 
section.
    (3) A person who submits information to EPA under this part must 
reassert a claim of confidentiality and substantiate the claim each 
time the information is submitted to EPA.
    (c) Any person asserting a claim of confidentiality under this part 
must substantiate each claim in accordance with the requirements in 
Sec. 725.94.
    (d) EPA will disclose information that is subject to a claim of 
confidentiality asserted under this section only to the extent 
permitted by the Act, this subpart, and part 2 of this title.

[[Page 17941]]

    (e) If a submitter does not assert a claim of confidentiality for 
information at the time it is submitted to EPA, EPA may make the 
information public and place it in the public file without further 
notice to the submitter.


Sec. 725.85  Microorganism identity.

    (a) Claims applicable to the period prior to commencement of 
manufacture or import for general commercial use--(1) When to make a 
claim. (i) A person who submits information to EPA under this part may 
assert a claim of confidentiality for portions of the specific 
microorganism identity at the time of submission of the information. 
This claim will apply only to the period prior to the commencement of 
manufacture or import for general commercial use.
    (ii) A person who submits information to EPA under this part must 
reassert a claim of confidentiality and substantiate the claim each 
time the information is submitted to EPA. For example, if a person 
claims certain information confidential in a TERA submission and wishes 
the same information to remain confidential in a subsequent TERA or 
MCAN submission, the person must reassert and resubstantiate the claim 
in the subsequent submission.
    (2) Assertion of claim. (i) A submitter may assert a claim of 
confidentiality only if the submitter believes that public disclosure 
prior to commencement of manufacture or import for general commercial 
use of the fact that anyone is initiating research and development 
activities pertaining to the specific microorganism or intends to 
manufacture or import the specific microorganism for general commercial 
use would reveal confidential business information. Claims must be 
substantiated in accordance with the requirements of Sec. 725.94(a).
    (ii) If the submission includes a health and safety study 
concerning the microorganism and if the claim for confidentiality with 
respect to the specific identity is denied in accordance with 
Sec. 725.92(c), EPA will deny a claim asserted under paragraph (a) of 
this section.
    (3) Development of generic name. Any person who asserts a claim of 
confidentiality for portions of the specific microorganism identity 
under this paragraph must provide one of the following items at the 
time the submission is filed:
    (i) The generic name which was accepted by EPA in the prenotice 
consultation conducted under paragraph (a)(4) of this section.
    (ii) One generic name that is only as generic as necessary to 
protect the confidential identity of the particular microorganism. The 
name should reveal the specific identity to the maximum extent 
possible. The generic name will be subject to EPA review and approval.
    (4) Determination by EPA. (i) Any person who intends to assert a 
claim of confidentiality for the specific identity of a new 
microorganism may seek a determination by EPA of an appropriate generic 
name for the microorganism before filing a submission. For this 
purpose, the person should submit to EPA:
    (A) The specific identity of the microorganism.
    (B) A proposed generic name(s) which is only as generic as 
necessary to protect the confidential identity of the new 
microorganism. The name(s) should reveal the specific identity of the 
microorganism to the maximum extent possible.
    (ii) Within 30 days, EPA will inform the submitter either that one 
of the proposed generic names is adequate or that none is adequate and 
further consultation is necessary.
    (5) Use of generic name. If a submitter claims microorganism 
identity as confidential under paragraph (a) of this section, and if 
the submitter complies with paragraph (a)(2) of this section, EPA will 
issue for publication in the Federal Register notice described in 
Sec. 725.40 the generic name proposed by the submitter or one agreed 
upon by EPA and the submitter.
    (b) Claims applicable to the period after commencement of 
manufacture or import for general commercial use--(1) Maintaining 
claim. Any claim of confidentiality under paragraph (a) of this section 
is applicable only until the microorganism is manufactured or imported 
for general commercial use and becomes eligible for inclusion on the 
Inventory. To maintain the confidential status of the microorganism 
identity when the microorganism is added to the Inventory, a submitter 
must reassert the confidentiality claim and substantiate the claim in 
the notice of commencement of manufacture required under Sec. 725.190.
    (i) A submitter may not claim the microorganism identity 
confidential for the period after commencement of manufacture or import 
for general commercial use unless the submitter claimed the 
microorganism identity confidential under paragraph (a) of this section 
in the MCAN submitted for the microorganism.
    (ii) A submitter may claim the microorganism identity confidential 
for the period after commencement of manufacture or import for general 
commercial use if the submitter did not claim the microorganism 
identity confidential under paragraph (a) of this section in any TERA 
submitted for the microorganism, but subsequently did claim 
microorganism identity confidential in the MCAN submitted for the 
microorganism.
    (2) Assertion of claim. (i) A person who believes that public 
disclosure of the fact that anyone manufactures or imports the 
microorganism for general commercial use would reveal confidential 
business information may assert a claim of confidentiality under 
paragraph (b) of this section.
    (ii) If the notice includes a health and safety study concerning 
the new microorganism, and if the claim for confidentiality with 
respect to the microorganism identity is denied in accordance with 
Sec. 725.92(c), EPA will deny a claim asserted under paragraph (b) of 
this section.
    (3) Requirements for assertion. Any person who asserts a 
confidentiality claim for microorganism identity must:
    (i) Comply with the requirements of paragraph (a)(3) of this 
section regarding submission of a generic name.
    (ii) Agree that EPA may disclose to a person with a bona fide 
intent to manufacture or import the microorganism the fact that the 
particular microorganism is included on the confidential Inventory for 
purposes of notification under section 5(a)(1)(A) of the Act.
    (iii) Have available and agree to furnish to EPA upon request the 
taxonomic designations and supplemental information required by 
Sec. 725.12.
    (iv) Provide a detailed written substantiation of the claim, in 
accordance with the requirements of Sec. 725.94(b).
    (4) Denial of claim. If the submitter does not meet the 
requirements of paragraph (b) of this section, EPA will deny the claim 
of confidentiality.
    (5) Acceptance of claim. (i) EPA will publish a generic name on the 
public Inventory if:
    (A) The submitter asserts a claim of confidentiality in accordance 
with this paragraph.
    (B) No claim for confidentiality of the microorganism identity as 
part of a health and safety study has been denied in accordance with 
part 2 of this title or Sec. 725.92.
    (ii) Publication of a generic name on the public Inventory does not 
create a category for purposes of the Inventory. Any person who has a 
bona fide intent to manufacture or import a microorganism which is 
described by a generic name on the public Inventory may submit an 
inquiry to EPA under

[[Page 17942]]

Sec. 725.15(b) to determine whether the particular microorganism is 
included on the confidential Inventory.
    (iii) Upon receipt of a request described in Sec. 725.15(b), EPA 
may require the submitter who originally asserted confidentiality for a 
microorganism to submit to EPA the information listed in paragraph 
(b)(3)(iii) of this section.
    (iv) Failure to submit any of the information required under 
paragraph (b)(3)(iii) of this section within 10 calendar days of 
receipt of a request by EPA under paragraph (b) of this section will 
constitute a waiver of the original submitter's confidentiality claim. 
In this event, EPA may place the specific microorganism identity on the 
public Inventory without further notice to the original submitter.
    (6) Use of generic name on the public Inventory. If a submitter 
asserts a claim of confidentiality under paragraph (b) of this section, 
EPA will examine the generic microorganism name proposed by the 
submitter.
    (i) If EPA determines that the generic name proposed by the 
submitter is only as generic as necessary to protect the confidential 
identity of the particular microorganism, EPA will place that generic 
name on the public Inventory.
    (ii) If EPA determines that the generic name proposed by the 
submitter is more generic than necessary to protect the confidential 
identity, EPA will propose in writing, for review by the submitter, an 
alternative generic name that will reveal the identity of the 
microorganism to the maximum extent possible.
    (iii) If the generic name proposed by EPA is acceptable to the 
submitter, EPA will place that generic name on the public Inventory.
    (iv) If the generic name proposed by EPA is not acceptable to the 
submitter, the submitter must explain in detail why disclosure of that 
generic name would reveal confidential business information and propose 
another generic name which is only as generic as necessary to protect 
the confidential identity of the microorganism. If EPA does not receive 
a response from the submitter within 30 days after the submitter 
receives the proposed name, EPA will place EPA's chosen generic name on 
the public Inventory. If the submitter does provide the information 
requested, EPA will review the response. If the submitter's proposed 
generic name is acceptable, EPA will publish that generic name on the 
public Inventory. If the submitter's proposed generic name is not 
acceptable, EPA will notify the submitter of EPA's choice of a generic 
name. Thirty days after this notification, EPA will place the chosen 
generic name on the public Inventory.


Sec. 725.88   Uses of a microorganism.

    (a) Assertion of claim. A person who submits information to EPA 
under this part on the categories or proposed categories of use of a 
microorganism may assert a claim of confidentiality for this 
information.
    (b) Requirements for claim. A submitter that asserts such a claim 
must:
    (1) Report the categories or proposed categories of use of the 
microorganism.
    (2) Provide, in nonconfidential form, a description of the uses 
that is only as generic as necessary to protect the confidential 
business information. The generic use description will be included in 
the Federal Register notice described in Sec. 725.40.
    (c) Generic use description. The person must submit the information 
required by paragraph (b) of this section by describing the uses as 
precisely as possible, without revealing the information which is 
claimed confidential, to disclose as much as possible how the use may 
result in human exposure to the microorganism or its release to the 
environment.


Sec. 725.92   Data from health and safety studies of microorganisms.

    (a) Information other than specific microorganism identity. Except 
as provided in paragraph (b) of this section, EPA will deny any claim 
of confidentiality with respect to information included in a health and 
safety study of a microorganism, unless the information would disclose 
confidential business information concerning:
    (1) Processes used in the manufacture or processing of a 
microorganism.
    (2) Information which is not in any way related to the effects of a 
microorganism on health or the environment, such as, the name of the 
submitting company, cost or other financial data, product development 
or marketing plans, and advertising plans, for which the person submits 
a claim of confidentiality in accordance with Sec. 725.80.
    (b) Microorganism identity--(1) Claims applicable to the period 
prior to commencement of manufacture or import for general commercial 
use. A claim of confidentiality for the period prior to commencement of 
manufacture or import for general commercial use for the specific 
identity of a microorganism for which a health and safety study was 
submitted must be asserted in conjunction with a claim asserted under 
Sec. 725.85(a). The submitter must substantiate each claim in 
accordance with the requirements of Sec. 725.94(a).
    (2) Claims applicable to the period after commencement of 
manufacture or import for general commercial use. To maintain the 
confidential status of the specific identity of a microorganism for 
which a health and safety study was submitted after commencement of 
manufacture or import for general commercial use, the claim must be 
reasserted and substantiated in conjunction with a claim under 
Sec. 725.85(b). The submitter must substantiate each claim in 
accordance with the requirements of Sec. 725.94(b).
    (c) Denial of confidentiality claim. EPA will deny a claim of 
confidentiality for microorganism identity under paragraph (b) of this 
section, unless:
    (1) The information would disclose processes used in the 
manufacture or processing of a microorganism.
    (2) The microorganism identity is not necessary to interpret a 
health and safety study.
    (d) Use of generic names. When EPA discloses a health and safety 
study containing a microorganism identity, which the submitter has 
claimed confidential, and if the Agency has not denied the claim under 
paragraph (c) of this section, EPA will identify the microorganism by 
the generic name selected under Sec. 725.85.


Sec. 725.94   Substantiation requirements.

    (a) Claims applicable to the period prior to commencement of 
manufacture or import for general commercial use--(1) MCAN, TME, Tier I 
certification, and Tier II exemption request requirements. Any person 
who submits a MCAN, TME, Tier I certification, or Tier II exemption 
request should strictly limit confidentiality claims to that 
information which is confidential and proprietary to the business.
    (i) If any information in the submission is claimed as confidential 
business information, the submitter must substantiate each claim by 
submitting written answers to the questions in paragraphs (c), (d), and 
(e) of this section at the time the person submits the information.
    (ii) If the submitter does not provide written substantiation as 
required in paragraph (a)(1)(i) of this section, the submission will be 
considered incomplete and the review period will not begin in 
accordance with Sec. 725.33.
    (2) TERA requirements. Any person who submits a TERA, should 
strictly limit confidentiality claims to that information which is 
confidential and proprietary to the business. If any information in 
such a submission is claimed as confidential business information, the 
submitter must have available for each of those claims, and

[[Page 17943]]

agree to furnish to EPA upon request, written answers to the questions 
in paragraphs (d) and (e) of this section.
    (b) Claims applicable to the period after commencement of 
manufacture or import for general commercial use. (1) If a submitter 
claimed portions of the microorganism identity confidential in the MCAN 
and wants the identity to be listed on the confidential Inventory, the 
claim must be reasserted and substantiated at the time the Notice of 
Commencement (NOC) is submitted under Sec. 725.190. Otherwise, EPA will 
list the specific microorganism identity on the public Inventory.
    (2) The submitter must substantiate the claim for confidentiality 
of the microorganism identity by answering all of the questions in 
paragraphs (c), (d), and (e) in this section. In addition, the 
following questions must be answered:
    (i) What harmful effects to the company's or institution's 
competitive position, if any, would result if EPA publishes on the 
Inventory the identity of the microorganism? How could a competitor use 
such information given the fact that the identity of the microorganism 
otherwise would appear on the TSCA Inventory with no link between the 
microorganism and the company or institution? How substantial would the 
harmful effects of disclosure be? What is the causal relationship 
between the disclosure and the harmful effects?
    (ii) Has the identity of the microorganism been kept confidential 
to the extent that competitors do not know it is being manufactured or 
imported for general commercial use by anyone?
    (c) General questions. The following questions must be answered in 
detail for each confidentiality claim:
    (1) For what period of time is a claim of confidentiality being 
asserted? If the claim is to extend until a certain event or point in 
time, indicate that event or time period. Explain why the information 
should remain confidential until such point.
    (2) Briefly describe any physical or procedural restrictions within 
the company or institution relating to the use and storage of the 
information claimed as confidential. What other steps, if any, apply to 
use or further disclosure of the information?
    (3) Has the information claimed as confidential been disclosed to 
individuals outside of the company or institution? Will it be disclosed 
to such persons in the future? If so, what restrictions, if any, apply 
to use or further disclosure of the information?
    (4) Does the information claimed as confidential appear, or is it 
referred to, in any of the following questions? If the answer is yes to 
any of these questions, indicate where the information appears and 
explain why it should nonetheless be treated as confidential.
    (i) Advertising or promotional materials for the microorganism or 
the resulting end product?
    (ii) Material safety data sheets or other similar materials for the 
microorganism or the resulting end product?
    (iii) Professional or trade publications?
    (iv) Any other media available to the public or to competitors?
    (v) Patents?
    (vi) Local, State, or Federal agency public files?
    (5) Has EPA, another Federal agency, a Federal court, or a State 
made any confidentiality determination regarding the information 
claimed as confidential? If so, provide copies of such determinations.
    (6) For each type of information claimed confidential, describe the 
harm to the company's or institution's competitive position that would 
result if this information were disclosed. Why would this harm be 
substantial? How could a competitor use such information? What is the 
causal connection between the disclosure and harm?
    (7) If EPA disclosed to the public the information claimed as 
confidential, how difficult would it be for the competitor to enter the 
market for the resulting product? Consider such constraints as capital 
and marketing cost, specialized technical expertise, or unusual 
processes.
    (d) Microorganism identity and production method. If 
confidentiality claims are asserted for the identity of the 
microorganism or information on how the microorganism is produced, the 
following questions must be answered:
    (1) Has the microorganism or method of production been patented in 
the U.S. or elsewhere? If so, why is confidentiality necessary?
    (2) Does the microorganism leave the site of production or testing 
in a form which is accessible to the public or to competitors? What is 
the cost to a competitor, in time and money, to develop appropriate use 
conditions? What factors facilitate or impede product analysis?
    (3) For each additional type of information claimed as 
confidential, explain what harm would result from disclosure of each 
type of information if the identity of the microorganism were to remain 
confidential.
    (e) Health and safety studies of microorganisms. If confidentiality 
claims are asserted for information in a health or safety study of a 
microorganism, the following questions must be answered:
    (1) Would the disclosure of the information claimed confidential 
reveal: confidential process information, or information unrelated to 
the effects of the microorganism on health and the environment. 
Describe the causal connection between the disclosure and harm.
    (2) Does the company or institution assert that disclosure of the 
microorganism identity is not necessary to interpret any health and 
safety studies which have been submitted? If so, explain how a less 
specific identity would be sufficient to interpret the studies.


Sec. 725.95   Public file.

    All information submitted, including any health and safety study of 
a microorganism and other supporting documentation, will become part of 
the public file for that submission, unless such materials are claimed 
confidential. In addition, EPA may add materials to the public file, 
unless such materials are claimed confidential. Any of the 
nonconfidential material described in this subpart will be available 
for public inspection in the TSCA Public Docket Office, Rm. NE-B607, 
401 M St., SW., Washington, DC, between the hours of noon to 4 p.m., 
Monday through Friday, excluding legal holidays.
Subpart D--Microbial Commercial Activities Notification Requirements


Sec. 725.100   Scope and purpose.

    (a) This subpart establishes procedures for submission of a notice 
to EPA under section 5(a) of the Act for persons who manufacture, 
import, or process microorganisms for commercial purposes. This notice 
is called a Microbial Commercial Activity Notice (MCAN). It is expected 
that MCANs will in general only be submitted for microorganisms 
intended for general commercial use. Persons who manufacture, import, 
or process a microorganism in small quantities solely for research and 
development as defined in Sec. 725.3 are not required to submit a 
notice to EPA. Persons who manufacture, import, or process a 
microorganism for research and development activities that do not fit 
the definition of small quantities solely for research and development 
may nonetheless qualify for more limited reporting requirements in 
Subpart E, including the TERA which can be used for review of research 
and development involving environmental release.
    (b) Persons subject to MCAN submission are described in 
Sec. 725.105.

[[Page 17944]]

    (c) Exclusions and exemptions specific to MCAN submissions are 
described in Sec. 725.110.
    (d) Submission requirements applicable specifically to MCANs are 
described at Sec. 725.150.
    (e) Data requirements for MCANs are set forth in Secs. 725.155 and 
725.160.
    (f) EPA review procedures specific to MCANs are set forth in 
Sec. 725.170.
    (g) Subparts A through C of this part apply to any MCAN submitted 
under this subpart.


Sec. 725.105   Persons who must report.

    (a) Manufacturers of new microorganisms. (1) MCAN submission is 
required for any person who intends to manufacture for commercial 
purposes in the United States a new microorganism. Exclusions are 
described in Sec. 725.110.
    (2) If a person contracts with a manufacturer to produce or process 
a new microorganism and the manufacturer produces or processes the 
microorganism exclusively for that person, and that person specifies 
the identity of the microorganism, and controls the total amount 
produced and the basic technology for the plant process, then that 
person must submit the MCAN. If it is unclear who must report, EPA 
should be contacted to determine who must submit the MCAN.
    (3) Only manufacturers that are incorporated, licensed, or doing 
business in the United States may submit a MCAN.
    (b) Importers of new microorganisms. (1) MCAN submission is 
required for a person who intends to import into the United States for 
commercial purposes a new microorganism. Exclusions are described in 
Sec. 725.110.
    (2) When several persons are involved in an import transaction, the 
MCAN must be submitted by the principal importer. If no one person fits 
the principal importer definition in a particular transaction, the 
importer should contact EPA to determine who must submit the MCAN for 
that transaction.
    (3) Except as otherwise provided in paragraph (b)(4) of this 
section, the provisions of this subpart D apply to each person who 
submits a MCAN for a new microorganism which such person intends to 
import for a commercial purpose. In addition, each importer must comply 
with paragraph (b)(4) of this section.
    (4) EPA will hold the principal importer, or the importer that EPA 
determines must submit the MCAN when there is no principal importer 
under paragraph (b)(2) of this section, liable for complying with this 
part, for completing the MCAN, and for the completeness and 
truthfulness of all information which it submits.
    (c) Manufacturers, importers, or processors of microorganisms for a 
significant new use. MCAN submission is required for any person who 
intends to manufacture, import, or process for commercial purposes a 
microorganism identified as having one or more significant new uses in 
subpart M of this part, and who intends either to engage in a 
designated significant new use of the microorganism or intends to 
distribute it in commerce. Persons excluded from reporting on 
significant new uses of microorganisms and additional procedures for 
reporting are described in subpart L of this part.


Sec. 725.110   Persons not subject to this subpart.

    Persons are not subject to the requirements of this subpart for the 
following activities:
    (a) Manufacturing, importing, or processing solely for research and 
development microorganisms that meet the requirements for an exemption 
under subpart E of this part.
    (b) Manufacturing, importing, or processing microorganisms for test 
marketing activities which have been granted an exemption under subpart 
F of this part.
    (c) Manufacturing or importing new microorganisms under the 
conditions of a Tier I or Tier II exemption under subpart G of this 
part.


Sec. 725.150   Procedural requirements for this subpart.

    General requirements for all MCANs under this part are contained in 
subparts A through C of this part. In addition, the following 
requirements apply to MCANs submitted under this subpart:
    (a) When to submit a MCAN. A MCAN must be submitted at least 90 
calendar days prior to manufacturing or importing a new microorganism 
and at least 90 calendar days prior to manufacturing, importing, or 
processing a microorganism for a significant new use.
    (b) Section 5(b) of the Act. The submitter must comply with any 
applicable requirement of section 5(b) of the Act for the submission of 
test data.
    (c) Contents of a MCAN. Each person who submits a MCAN under this 
subpart must provide the information and test data described in 
Secs. 725.155 and 725.160.
    (d) Recordkeeping. Each person who submits a MCAN under this 
subpart must comply with the recordkeeping requirements of Sec. 725.65.


Sec. 725.155   Information to be included in the MCAN.

    (a) Each person who is required by this part to submit a MCAN must 
include the information specified in paragraphs (c) through (h) of this 
section, to the extent it is known to or reasonably ascertainable by 
that person. However, no person is required to include information 
which relates solely to exposure of humans or ecological populations 
outside of the United States.
    (b) Each person should also submit, in writing, all other 
information known to or reasonably ascertainable by that person that 
would permit EPA to make a reasoned evaluation of the health and 
environmental effects of the microorganism, or any microbial mixture or 
article, including information on its effects on humans, animals, 
plants, and other microorganisms, and in the environment. The 
information to be submitted under this subpart includes the information 
listed in paragraphs (c) through (h) of this section relating to the 
manufacture, processing, distribution in commerce, use, and disposal of 
the new microorganism.
    (c) 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.
    (d) Microorganism identity information. Persons must submit 
sufficient information to allow the microorganism to be accurately and 
unambiguously identified for listing purposes as required by 
Sec. 725.12.
    (1) Description of the recipient microorganism and the new 
microorganism. (i) Data substantiating the taxonomy of the recipient 
microorganism and the new microorganism to the level of strain, as 
appropriate. In lieu of data, EPA will accept a letter from a culture 
collection substantiating taxonomy, provided EPA, upon request to the 
submitter, may have access to the data supporting the taxonomic 
designation.
    (ii) Information on the morphological and physiological features of 
the new microorganism.
    (iii) Other specific data by which the new microorganism may be 
uniquely identified for Inventory purposes.
    (2) Genetic construction of the new microorganism. (i) Data 
substantiating the taxonomy of the donor organism(s). In lieu of data, 
EPA will accept a letter from a culture collection substantiating 
taxonomy, provided EPA, upon request to the submitter, may have access 
to the

[[Page 17945]]

data supporting the taxonomic designation.
    (ii) Description of the traits for which the new microorganism has 
been selected or developed and other traits known to have been added or 
modified.
    (iii) A detailed description of the genetic construction of the new 
microorganism, including the technique used to modify the microorganism 
(e.g., fusion of cells, injection of DNA, electroporation or chemical 
poration, or methods used for induced mutation and selection). The 
description should include, for example, a description of the 
introduced genetic material, including any regulatory sequences and 
structural genes and the products of those genes; how the introduced 
genetic material is expected to affect behavior of the recipient; 
expression, alteration, and stability of the introduced genetic 
material; methods for vector construction and introduction; and a 
description of the regulatory and structural genes that are components 
of the introduced genetic material, including genetic maps of the 
introduced sequences.
    (3) Phenotypic and ecological characteristics. (i) Habitat, 
geographical distribution, and source of the recipient microorganism.
    (ii) Survival and dissemination under relevant environmental 
conditions including a description of methods for detecting the new or 
recipient microorganism(s) in the environment and the sensitivity limit 
of detection for these techniques.
    (iii) A description of anticipated biological interactions with and 
effects on target organisms and other organisms such as competitors, 
prey, hosts, symbionts, parasites, and pathogens; a description of host 
range; a description of pathogenicity, infectivity, toxicity, 
virulence, or action as a vector of pathogens; and capacity for genetic 
transfer under laboratory and relevant environmental conditions.
    (iv) A description of anticipated involvement in biogeochemical or 
biological cycling processes, involvement in rate limiting steps in 
mineral or nutrient cycling, or involvement in inorganic compounds 
cycling (such as possible sequestration or transformation of heavy 
metals).
    (e) Byproducts. A description of the byproducts resulting from the 
manufacture, processing, use, and disposal of the new microorganism.
    (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 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.


Sec. 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 Sec. 725.25(h), and in 
addition to the information required by Sec. 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.
    (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

[[Page 17946]]

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 Sec. 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 Sec. 725.25(h), and in 
addition to the information required by Sec. 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.
    (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.


Sec. 725.170   EPA review of the MCAN.

    General procedures for review of all submissions under this part 
are contained in Secs. 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 Sec. 725.33, unless the Agency extends the period under 
section 5(c) of the Act and Sec. 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.


Sec. 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.
    (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 Sec. 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 Sec. 725.25(c).
Subpart E--Exemptions for Research and Development Activities


Sec. 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 Sec. 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 Secs. 725.232, 
725.234, and 725.238.
    (d) Submission requirements specific for TERAs are described at 
Sec. 725.250.
    (e) Data requirements for TERAs are set forth in Secs. 725.255 and 
725.260.

[[Page 17947]]

    (f) EPA review procedures specific for TERAs are set forth in 
Secs. 725.270 and 725.288.
    (g) Subparts A through C of this part apply to any submission under 
this subpart.


Sec. 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 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 
Secs. 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 
Sec. 172.45(c), or
    (2) The person is manufacturing a microbial pesticide for which an 
Experimental Use Permit is required, pursuant to Sec. 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.


Sec. 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 Sec. 725.3.
    (c)(1) The person receives research funds from another Federal 
agency, and the funds are 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.


Sec. 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 Sec. 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 Sec. 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 Sec. 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

[[Page 17948]]

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 Sec. 725.235(a), 
which may be associated with the microorganism. The notification must 
be made in accordance with Sec. 725.235(b).


Sec. 725.235   Conditions of exemption for activities conducted inside 
a structure.

    (a) Determination of risks. To determine whether notification under 
Sec. 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 
Sec. 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 
Sec. 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 
Sec. 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 Sec. 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 standard laboratory records, 
shall satisfy the recordkeeping requirement specified in 
Sec. 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 
Sec. 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 Sec. 725.234(d)(3) and certification 
by an authorized official required by Sec. 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.


Sec. 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 Sec. 725.239 may be conducted without prior review by EPA if all of 
the conditions of this section and Sec. 725.239 are met.
    (2) The research and development activity involving a microorganism 
listed in Sec. 725.239 must be conducted by, or directly under the 
supervision of, a technically qualified individual, as defined in 
Sec. 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 Sec. 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 Sec. 725.65 and retain documentation that supports 
their compliance with the requirements of this section and the specific 
requirements for the microorganism listed in Sec. 725.239.

[[Page 17949]]

Sec. 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 
Sec. 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 Sec. 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.
    (ii) The technically qualified individual must select appropriate 
methods to limit the dissemination of modified Rhizobium meliloti.


Sec. 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 
Secs. 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 Sec. 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 Sec. 725.25(c) 
within 1 year of the termination of the activity.


Sec. 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 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 Sec. 725.155(c), (d)(1), and (d)(2).
    (d) Persons applying for a TERA must submit phenotypic and 
ecological characteristics information required in Sec. 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,

[[Page 17950]]

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.


Sec. 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 
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 
Sec. 725.160(a)(3) and (b)(3).


Sec. 725.270   EPA review of the TERA.

    General procedures for review of all submissions under this part 
are contained in Secs. 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 Sec. 725.33, unless 
EPA finds good cause for an extension under Sec. 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.


Sec. 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

[[Page 17951]]

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 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


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


Sec. 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.


Sec. 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 Sec. 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.


Sec. 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 Sec. 725.155(c), (d)(1), and (d)(2).
    (d) Persons applying for a TME must submit phenotypic and 
ecological characteristics information required in Sec. 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 Sec. 725.160.


Sec. 725.370   EPA review of the TME application.

    General procedures for review of all submissions under this part 
are contained in Secs. 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 a result 
of test marketing.
Subpart G--General Exemptions for New Microorganisms


Sec. 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 Sec. 725.420.
    (c) Criteria for the introduced genetic material contained in the 
new microorganisms are described in Sec. 725.421.
    (d) Physical containment and control technologies are described in 
Sec. 725.422.
    (e) The conditions for the Tier I exemption are listed in 
Sec. 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

[[Page 17952]]

exemption request. The limited reporting requirements for the Tier II 
exemption, including data requirements, are described in Secs. 725.450 
and 725.455.
    (g) EPA review procedures for the Tier II exemption are set forth 
in Sec. 725.470.
    (h) Subparts A through C of this part apply to any submission under 
this subpart.


Sec. 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.


Sec. 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, 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 those 
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.
    (2) Sequences for protein synthesis inhibitor.

                                                                        
                                                                        
              Sequence Source                        Toxin Name         
                                                                        
Corynebacterium diphtheriae & C. ulcerans   Diphtheria toxin            
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                
                                                                        
  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                  
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                 

[[Page 17953]]

                                                                        
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)     
                                                                        

    (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         Leucocidin (leukocidin,     
 aeruginosa                                  cytotoxin)                 
Streptococcus pyogenes                      Streptolysin S (SLS);       
                                             Erythrogenic toxins        
                                             (scarlet fever toxins,     
                                             pyrogenic exotoxins)       
Yersinia enterocolitica                     Heat-stable enterotoxins    
                                             (ST)                       
                                                                        

Sec. 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.


Sec. 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 Sec. 725.420.
    (2) The introduced genetic material meets the criteria under 
Sec. 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 Sec. 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 Sec. 725.420.
    (5) The manufacturer or importer complies with the recordkeeping 
requirements of Sec. 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 Sec. 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 Sec. 725.421.

[[Page 17954]]

    (ii) Compliance with the containment requirements described in 
Sec. 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 Sec. 725.25(b). 
Certification of submission of test data is not required for the Tier I 
exemption.


Sec. 725.426   Applicability of the Tier I exemption.

    The Tier I exemption under Sec. 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 
Secs. 725.420, 725.421, and 725.422.


Sec. 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 Sec. 725.420.
    (b) The introduced genetic material meets the criteria under 
Sec. 725.421.
    (c) Adequate physical containment and control technologies are 
used. The criteria listed under Sec. 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 
Sec. 725.455(d). EPA will review proposed process and containment 
procedures as part of the submission for a Tier II exemption under this 
section.


Sec. 725.450   Procedural requirements for the Tier II exemption.

    General requirements for all submissions under this part are 
contained in Sec. 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 Secs. 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 Sec. 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.


Sec. 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 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 Sec. 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 Sec. 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 Sec. 725.25(b). 
Certification of submission of test data is not required for the Tier 
II exemption.


Sec. 725.470   EPA review of the Tier II exemption request.

    General procedures for review of all submissions under this part 
are contained in Secs. 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 Sec. 725.33, 
unless the Agency extends the review period for good cause under 
Sec. 725.56.
    (b) Criteria for review. EPA will review the request to determine 
that the new microorganism complies with Sec. 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 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 Sec. 725.428 or the

[[Page 17955]]

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


Sec. 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 
Sec. 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 Secs. 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 Sec. 725.950.
    (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 Secs. 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.


Sec. 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:
    (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, 401 M St., SW., Washington, DC 20460.

[[Page 17956]]

    (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.


Sec. 725.912   Exemptions.

    Persons identified in Sec. 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 Secs. 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, 
Secs. 725.105 and 725.910 apply and Sec. 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.


Sec. 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 Secs. 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.


Sec. 725.950   Additional recordkeeping requirements.

    Persons submitting a MCAN for a significant new use of a 
microorganism must comply with the recordkeeping requirements of 
Sec. 725.65. In addition, the following requirements apply:
    (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.


Sec. 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, 401 M St., SW., 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.

[[Page 17957]]

    (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 submitted.
    (7) The data and information described in Secs. 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.


Sec. 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 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.

[[Page 17958]]

    (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 within 180 days of receipt of a valid notice of 
commencement under Sec. 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.


Sec. 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 Sec. 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 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 Sec. 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 Sec. 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, 401 M St., SW., 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


Sec. 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.

[FR Doc. 97-8669 Filed 4-10-97; 8:45 am]
BILLING CODE 6560-50-F