[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
_______________________________________________________________________
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-Hotline@epamail.epa.gov.
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
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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.
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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-
Hotline@epamail.epa.gov.
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
