[Federal Register Volume 59, Number 169 (Thursday, September 1, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-21359]
[[Page Unknown]]
[Federal Register: September 1, 1994]
_______________________________________________________________________
Part III
Environmental Protection Agency
_______________________________________________________________________
40 CFR Part 700, et al.
Microbial Products of Biotechnology; Proposed Regulation Under the
Toxic Substances Control Act; Proposed Rule
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Parts 700, 720, 721, 723, and 725
[OPPTS-00049c; FRL-4778-4]
RIN 2070-AB61
Microbial Products of Biotechnology; Proposed Regulation Under
the Toxic Substances Control Act
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
-----------------------------------------------------------------------
SUMMARY: EPA is proposing this regulation under section 5 of the Toxic
Substances Control Act (TSCA), 15 U.S.C 2604, to screen microorganisms
before they are introduced into commerce. Under an interpretation EPA
issued in 1986 (51 FR 23302, June 26, 1986), ``new'' microorganisms are
those formed by deliberate combinations of genetic material from
organisms in different genera. This proposed rule is designed to
prevent unreasonable risk to human health and the environment without
imposing unnecessary regulatory burdens on the biotechnology industry.
This proposed regulation describes notification procedures and
microorganisms that would be exempt from notification.
DATES: Written comments on this proposed rule should be received by
October 31, 1994.
EPA may hold an informal hearing in Washington, DC, if EPA receives
written requests to hold a public hearing. For further information on
the hearing, see Unit IV.I. of this preamble. Written requests to make
an oral presentation should be submitted to the Environmental
Assistance Division by October 3, 1994 at the address below. Persons
are advised to call the Environmental Assistance Division after October
11, 1994 to ascertain if a hearing is to be held, and the date, time,
and location.
ADDRESSES: Comments on issues concerning this proposed rule should bear
the docket control number OPPTS-00049C, and should be submitted to the
following address: Document Processing Center (7407), Office of
Pollution Prevention and Toxics, Environmental Protection Agency, Rm.
L-100, 401 M St., SW., Washington, DC 20460.
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, Rm. EB-44, 401
M St., SW., Washington, DC 20460, In the USA: (202-554-1404), TDD:
(202-554-0551). For technical information regarding this document: Paul
Campanella, Office of Pollution Prevention Toxics (7405), Environmental
Protection Agency, Rm. E-611, 401 M St., SW., Washington, DC 20460, In
the USA: (202-260-3725).
SUPPLEMENTARY INFORMATION: The preamble accompanying this proposed rule
is divided into the following Units:
I. Introduction
A. Purpose of This Proposed Rule
B. Role of This Propose Rule in the Federal Coordinated
Framework for Regulation of Biotechnology
C. Statutory Framework
II. Structure of This Proposed Rule
A. Determining Whether Reporting is Required
B. General Administrative Procedures
C. Reporting General Commercial Use of TSCA Microorganisms
D. Reporting R&D Activities for TSCA Microorganisms
III. Rationale for Proposed Reporting Mechanisms
A. Research for Commercial Purposes
B. Exemption for Research in Contained Structures
C. Section 5(h)(4) Exemptions
IV. Other Issues
A. Microorganisms Covered By This Rulemaking
B. Listing Microorganisms on the Inventory
C. SNUR Process
D. Confidential Business Information
E. User Fees
F. Section 8(e) Reporting Requirements
G. Export Notification and State Preemption
H. Regulatory Text Overview
I. Rulemaking Process and Public Hearings
V. Economic Impact and Regulatory Flexibility Analysis
A. Regulatory Impact Analysis
B. Request for Comment on Economic Issues
VI. Rulemaking Record and Electronic Availability of Documents
VII. Public Record
VIII. References
IX. Regulatory Assessment Requirements
A. Executive Order 12866
B. Regulatory Flexibility Act
C. Paperwork Reduction Act
I. Introduction
A. Purpose of This Proposed Rule
This document proposes procedures for EPA to screen new
microorganisms. EPA's goals in proposing these rules are to take into
account scientific uncertainties surrounding the behavior of these
microorganisms and avoid unreasonable risks to health and the
environment which may be associated with their use, to avoid imposing
unwarranted costs and restrictions on a promising industry, and to
establish a flexible review program that can adjust as the technology
evolves and matures.
EPA will screen new microorganisms before they are manufactured for
general commercial use, or in some circumstances used for commercial
research and development (R&D) purposes, until sufficient familiarity
is gained with their behavior. As EPA acquires familiarity with new
microorganisms through reviews or other avenues, EPA expects certain of
these organisms to become eligible for reduced reporting or to be
eliminated from screening altogether.
EPA recognizes the enormous potential of biotechnology to fight
disease, pollution, and hunger, and to replace some chemicals that are
harmful to the environment. The realization of these benefits depends
upon public confidence in the safety of biotechnology. Public
perception will strongly affect the conduct of field tests and the
acceptance of commercial applications of biotechnology (Ref. 1). At the
same time, EPA recognizes the importance of retaining the competitive
advantage the United States presently maintains in the development and
application of biotechnology. Recognizing that regulations can affect
competitiveness and public acceptance either negatively or positively
(Ref. 2), EPA is proposing rules that it believes balance the needs of
the public without adversely affecting the capacity for innovation.
B. Role of This Proposed Rule in the Federal Coordinated Framework For
Regulation of Biotechnology
This proposed rule implements EPA's program for oversight of
microorganisms in accordance with the Federal ``Coordinated Framework
for Regulation of Biotechnology; Announcement of Policy and Notice for
Public Comment'' which was published by the Office of Science and
Technology Policy (OSTP) on June 26, 1986 (51 FR 23302, 23313). EPA's
policies regarding use of its statutes to regulate biotechnology
products are published 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 Coordinated Framework. EPA is currently
operating its biotechnology program under the 1986 Policy Statement.
Prior to the 1986 Policy Statement, EPA issued a ``Proposed Policy
Regarding Certain Microbial Products'' on December 31, 1984 (49 FR
50880) (``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
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 this
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 has been incorporated as
appropriate in this preamble, and summaries of subcommittee
deliberations have been placed in the docket for this rulemaking. This
proposed rule announced today is intended to describe implementation of
EPA's program for regulation of microorganisms under TSCA.
C. Statutory Framework
This Unit describes the TSCA provisions used for this rulemaking.
1. Jurisdiction. TSCA authorizes EPA to regulate any chemical
substance, except for certain substances covered by other Federal
agencies. The Act defines chemical substance broadly enough to cover
microorganisms. Specifically, section 3(2) of TSCA defines chemical
substance, in part, as any organic substance of a particular molecular
identity including any combination of such substances resulting in
whole or in part from a chemical reaction or occurring in nature.
a. Organisms are chemical substances. The TSCA definition of
chemical substance describes any deoxyribonucleic acid (DNA) or
ribonucleic acid (RNA) molecule, however created, that is a component
of an organism's genetic material. Similarly, a microorganism is a
chemical substance, because it is a combination of substances of
particular identities that occur in nature or occur, in whole or in
part, as a result of a chemical reaction (Ref. 3). EPA has consistently
applied this definition to life forms and in the 1984 Proposed Policy
Statement (49 FR 50886-87) clarified that this interpretation applies
to microorganisms. While the statutory term ``chemical substance'' has
been interpreted to include microorganisms, EPA acknowledges that
microorganisms are not generally referred to as chemicals. Therefore,
throughout this preamble, the term ``traditional chemicals'' will be
used to refer to chemical substances other than microorganisms.
The fact that microorganisms can be considered chemical substances
under TSCA only establishes EPA authority over them. Implementation of
that authority requires further action, either to interpret specific
terms or to issue rules. Discussion of the types of microorganisms
covered in this proposal can be found in Unit IV.A. of this preamble.
b. Plants and animals are not subject to this proposed rule. Plants
and animals could also be chemical substances under TSCA. Nevertheless,
as a matter of policy, EPA has limited this rulemaking to
microorganisms, e.g., microalgae of the plant kingdom. Transgenic
plants and animals are not subject to requirements under this proposed
rule, either as whole organisms or when their cells or parts of cells
are cultured in vitro. However, microorganisms into which plant or
animal gene segments are intentionally incorporated would be considered
microorganisms potentially subject to TSCA. Traditional chemicals
extracted from a plant or animal also may be subject to TSCA, as are
other chemical substances. EPA is reserving authority under TSCA to
screen transgenic plants and animals in the future as needed.
c. Microorganisms excluded by statute. The definition of ``chemical
substance'' in TSCA excludes pesticides, tobacco and tobacco products,
food, food additives, drugs (including human drugs, animal drugs, and
animal biologics), cosmetics, and substances that are used as medical
devices. These substances are regulated under other statutes by the EPA
Office of Pesticide Programs, the United States Department of
Agriculture (USDA), or the Food and Drug Administration (FDA).
Certain microorganisms that are subject to TSCA but are also known
plant pests are regulated jointly by EPA under TSCA and the USDA under
the Federal Plant Pest Act. In cases where microorganisms are not known
to be plant pests, the microorganisms used for TSCA purposes would be
regulated solely by EPA. However, USDA would become involved if an EPA
review determined that the microorganism had plant pest qualities.
d. Microorganisms used as intermediates. Microorganisms may be used
as intermediates to produce substances that are in turn used as
products subject to TSCA or other statutes. Under the Federal Food,
Drug, and Cosmetics Act (FFDCA), intermediates used to make products
subject to FFDCA are considered to be components of foods, food
additives, drugs, cosmetics and medical devices, as the case may be.
Therefore, those microorganism intermediates are excluded from
regulation under TSCA. All other intermediates, including pesticide
intermediates, are subject to TSCA jurisdiction. Traditional chemicals
not excluded from TSCA and produced by microorganism intermediates are
subject to TSCA section 5. These chemicals produced by microorganisms
are subject to the same requirements and procedures as chemicals
produced by other means. EPA discussed its approach to microorganism
intermediates and their products in its 1984 Proposed Policy Statement
(49 FR 50887, 50890; December 31, 1984).
2. Application of TSCA section 5. TSCA gives EPA comprehensive
authority to regulate chemical substances and mixtures of chemical
substances under four major provisions. Section 4 authorizes the
issuance of rules requiring testing of chemicals. Section 6 authorizes
the Agency to issue substantive regulations to protect against
chemicals that present an unreasonable risk. Section 7 authorizes
protection against imminent hazards. EPA has based its biotechnology
rulemaking efforts on section 5, the other major TSCA provision.
Section 5 establishes a 90-day process for EPA to screen certain
chemical substances before they are produced. Within the 90 days
following receipt of notification, EPA has to decide whether to drop
the substance from further consideration or to impose controls.
Section 5(a) allows EPA to require submission of a notification for
two types of microorganisms, those that are considered ``new'' chemical
substances and those that will be made for a ``significant new use.''
In both cases, notification is not triggered by a determination that a
risk is present. Risk is fully considered during or after the screening
process. Those substances defined as ``new chemical substances'' are
automatically subject to notice requirements. Chemical substances which
are made for a significant new use are subject to notification when EPA
issues a rule for the particular substance.
While the statute TSCA does not distinguish between the form or
content of the notifications for new substances or new uses, EPA's
current regulatory program, which is largely applicable to traditional
chemicals, does. The notification for a new chemical substance is
called a premanufacture notice (PMN). The notification for a
significant new use is called a significant new use notice (SNUN). For
the biotechnology program, however, EPA is proposing to refer to either
type of notification as a Microbial Commercial Activity Notice or MCAN.
Notices under section 5(a) are submitted by manufacturers of new
chemical substances, and by persons who manufacture or process chemical
substances for a significant new use. TSCA section 3(7) defines
``manufacture'' to mean import into the United States, production or
manufacture. Thus, the word manufacture as used in this preamble refers
to importation and any type of production, as well as to those
activities that may commonly be considered manufacture. TSCA section
3(10) defines ``process'' as preparation of a substance, after its
manufacture, for distribution in commerce.
a. Distinction between ``commercial purposes'' and ``general
commercial use.'' TSCA section 5(i) limits section 5 screening to
activities ``for commercial purposes.'' The term ``commercial
purposes'' applies to all activities that derive actual or potential
commercial benefit for persons associated with those activities. This
includes R&D designed to result in a commercial product, whether or not
a product is actually developed. A discussion of various options for
EPA to decide what constitutes commercial purposes under this rule
appears at Unit III.A.
These rules propose different review procedures for microorganisms
used for commercial R&D and for microorganisms that are no longer in
R&D and are intended for commercial distribution. In order to
distinguish between commercial R&D and other types of commercial
activity, EPA is describing use for commercial purposes beyond R&D as
``general commercial use.''
b. Definition of ``new.'' The term, ``new chemical substance,'' is
defined at TSCA section 3(9) as a substance not on the TSCA Inventory
of Chemical Substances (``Inventory'') manufactured in the United
States. Compilation and publication of the Inventory is a requirement
imposed on EPA by TSCA section 8(b). When EPA completes review of a new
substance, the substance is placed on the Inventory upon EPA's receipt
of a Notice of Commencement which indicates that production has begun.
At this point, the substance is no longer new, and subsequent producers
do not have to submit PMNs.
EPA has a longstanding policy of not explicitly listing on the
Inventory unprocessed naturally occurring substances. Instead, these
substances are considered to be implicitly included on the Inventory
(see 40 CFR 710.4(b)). Thus, they are not ``new'' and do not require
PMNs.
In defining what constitutes an unprocessed naturally occurring
substance, EPA has distinguished between substances isolated from
nature using more or less mechanical means and those isolated from
nature using more sophisticated forms of human intervention, such as
chemical reactions. The latter substances remove from a natural product
something that, by itself, does not exist in nature. One example is
that natural latex extracted from trees is a naturally occurring
substance, but the rubber formed after chemical coagulants are added is
not (42 FR 64589, December 23, 1977).
EPA is retaining for this rulemaking its interpretation of ``new''
microorganisms as discussed in the 1986 Policy Statement. Under that
interpretation, microorganisms resulting from deliberate, intergeneric
combinations of genetic material constitute ``new'' microorganisms
subject to PMN requirements. For the purposes of the Policy Statement,
the Agency defined intergeneric microorganisms as those formed by
deliberate combinations of genetic material from source organisms in
different genera. EPA may decide to reconsider its interpretation of
``new'' microorganism at a later time and in aseparate rulemaking. EPA
requests comment on whether it should explore alternative
interpretations of ``new'' microorganism.
In the 1986 Policy Statement, EPA excluded from the definition of a
``new'' microorganism, those microorganisms that have 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. EPA is also proposing to retain this exclusion as part of its
interpretation of ``new'' microorganism.
In the course of implementing the 1986 Policy Statement, the Agency
recognized that it had to develop additional guidance concerning the
definition of a new microorganism. It became apparent that a policy was
needed to address certain genetic elements which can be transferred
between microorganisms of different genera. These are termed mobile
genetic elements (MGEs) and include plasmids and transposons. EPA
developed additional guidance concerning whether microorganisms
modified using vectors that contained MGEs or parts of MGEs were
considered new. The Agency indicated that the major consideration is
the source of the original isolation of the MGE. EPA stated that
microorganisms would be considered ``new'' and thus subject to PMN
requirements, if the MGE was originally isolated from a microorganism
in a genus different from the recipient genus. Microorganisms would be
considered intrageneric, and hence not subject to PMN requirements, if
the MGE was originally isolated from a microorganism in the same genus
as the recipient.
The Agency has adopted this interpretation for reasons of
regulatory clarity and uncertainty about the possibility of the
resulting microorganism exhibiting new traits. For example, some MGEs
may contain genetic material that normally is not expressed in one
microorganism but, when inserted into another microorganism, may be
expressed and result in a new trait. Since the Agency plans to continue
to use the 1986 Policy Statement interpretation of ``new'' to be
intergeneric microorganisms, the Agency will continue to use this MGE
guidance to clarify what microorganisms would be subject to TSCA
section 5 reporting. EPA specifically requests comments on whether the
MGE interpretation provides appropriate assistance for determining
whether a microorganism is intergeneric or whether additional
modifications which would be useful in clarifying which intergeneric
microorganisms should be reported under TSCA section 5.
c. Significant new use. EPA determines a use is a significant new
use by issuing a rule. The rule is called a significant new use rule or
SNUR. Section 5(a)(2) sets forth some of the relevant considerations
for issuing a SNUR. The considerations generally include changes in the
type or form of exposure to a substance. Although EPA is not proposing
any specific SNURs in this rulemaking, EPA is proposing to set up
processes for issuing SNURs for microorganisms if needed in the future.
See Unit IV.C. of this preamble for a discussion of the proposed SNUR
processes.
d. Section 5 regulatory mechanisms. If the 90-day period provided
for review of a PMN or SNUN expires and EPA has taken no action,
production of the substance may begin. However, within the review
period, EPA may prevent or limit production of the substance under
section 5(e) or 5(f). Under section 5(e) EPA may issue an order
prohibiting or limiting production of a substance, if the Agency
determines that information is insufficient and the substance may
present unreasonable risk or its use may result in substantial
exposure. If the notification submitter objects, the section 5(e) order
does not take effect and EPA may go to court to obtain an injunction to
accomplish the same goals as the section 5(e) order.
Alternatively, if EPA finds that a substance presents or will
present an unreasonable risk, the Agency may, under section 5(f), go to
court for an order restricting or prohibiting production or issue an
administrative order or immediately effective rule to accomplish that
result.
If EPA decides subsequent to Inventory listing that further
oversight is needed, the Agency may use other provisions of TSCA. These
could include SNURs or other rules that would require testing (TSCA
section 4), information submission (TSCA section 8) or substantive
restrictions (TSCA section 6).
e. Exemptions from the section 5 notification process. Section 5(h)
provides for certain exemptions from screening. Three are relevant to
biotechnology. Section 5(h)(1) allows manufacturers or processors of
substances only for test marketing to apply to EPA for an exemption
from full notification. Unit II.C.3. of this preamble discusses the
test marketing exemption (TME) for microorganisms.
Section 5(h)(3) provides that the screening mechanisms do not apply
to substances manufactured or processed only in ``small quantities''
for R&D, provided that persons engaged in R&D activities for a
manufacturer are notified of any risks to health associated with the
substance. Section 5(h)(3) authorizes EPA to define by rule what
constitutes small quantities and to prescribe the form and manner of
risk notification. EPA is proposing a small quantities definition that
is limited to contained structure R&D uses of microorganisms. There
would be no small quantities exemption for microorganisms introduced
into the environment during commercial R&D, thus use of such
microorganisms must be reviewed. This modification is described at Unit
II.D. of this preamble. The rationale for this modification is
discussed at Unit III.B. of this preamble.
Section 5(h)(4) allows EPA to exempt new substances from all or
part of section 5 screening requirements, if the Agency determines, by
rule, that such substances will not present an unreasonable risk. EPA
is proposing to use section 5(h)(4) to exempt certain categories of
microorganisms from screening as new microorganisms. Additionally, EPA
is proposing under section 5(h)(4) to allow R&D introductions of
microorganisms into the environment on the condition that EPA has
approved them through expedited review of information submitted in a
TSCA Experimental Release Application, or TERA. The TERA process is
described in Unit II.D. of this preamble. EPA is also proposing other
section 5(h)(4) exemptions for specific microorganisms and classes of
microorganisms as described in Unit II.C. of this preamble. The
rationale for all exemptions proposed under section 5(h)(4) appears in
Unit III.C. of this preamble.
3. Substantial risk notification. Section 8(e) requires reporting
by manufacturers, processors and distributors who come across
information that their chemical substance could cause a ``substantial
risk.'' Section 8(e) is a self-implementing provision of TSCA. Thus, if
a manufacturer, processor or distributor of a microorganism finds
applicable information, that information must be submitted to EPA. Unit
IV.F. of this preamble discusses section 8(e) in further detail.
4. Applicability of TSCA section 26. Section 26(c) authorizes EPA
to take any action under TSCA for a category of chemical substances.
EPA proposes to use this authority extensively in this rule. The
reasons for grouping microorganisms into categories, which include new
microorganisms used for R&D and certain new microorganisms manufactured
for general commercial use, are explained in applicable sections.
II. Structure of the Proposed Rule
This portion of the preamble discusses the major provisions of
these rules. The rationale supporting these provisions follows in Unit
III. Unit II.A. describes how to determine whether reporting is
required. Unit II.B. describes general administrative procedures that
would be applicable to all notices submitted. To facilitate
understanding of this proposed rule, requirements for microorganisms
manufactured for general commercial use are discussed separately from
those for microorganisms used for commercial R&D. Unit II.C. describes
procedures applicable to microorganisms which are manufactured for
general commercial use. Unit II.D. contains a similar description of
procedures applicable to microorganisms used for R&D.
While these regulations are modelled after and incorporate many of
the procedures in the existing TSCA section 5 screening program for
traditional chemical substances which EPA has operated for the past
decade, modifications have been made, as appropriate, to address the
specific characteristics of microorganisms. In this respect, this
proposed rule incorporates well-established procedures which EPA has
adopted in previous rulemakings. The procedures are currently contained
in the Code of Federal Regulations (``CFR'') at parts 720
(premanufacture notification) and 721 (significant new use notification
requirements). EPA has decided, however, to establish a new part in the
CFR which applies specifically to microorganisms. EPA believes that
placing regulations affecting microorganisms screened under TSCA
section 5 in one place, part 725, will be more convenient and
efficient.
EPA has only made changes to the procedures in parts 720 and 721 to
the extent required by unique characteristics of microorganisms. EPA is
therefore not soliciting comment on the procedures in proposed part 725
that are incorporated from parts 720 and 721.
EPA will only consider comments to the extent they address the new
procedures and requirements in proposed part 725.
In addition to a preferred approach for certain issues, this
preamble often contains a discussion of alternatives. EPA solicits
public comment on the preferred approaches and the alternatives
discussed in this document. Depending on public comment received on the
various proposals, any of these alternatives may be adopted in the
final rules.
A. Determining Whether Reporting Is Required
Manufacturers or processors would follow the process laid out below
to determine whether their microorganism is subject to reporting and,
if it is, how it would be treated under this proposed rulemaking. They
must first determine whether their microbial products are subject to
TSCA. Subpart A of part 725 contains the regulations applicable to this
determination. Many microorganisms are not subject to the requirements
of this proposed rule, because they are statutorily outside the
jurisdiction of TSCA. Statutory jurisdiction is discussed in Unit I.C.
of this preamble.
1. Determining whether a microorganism is new or subject to a SNUR.
After manufacturers of microorganisms determine that their products are
subject to TSCA, they must determine whether the microorganisms are
new. Section 725.3 defines a new microorganism as one that is not
included on the Inventory. Microorganisms may be either implicitly or
explicitly included on the Inventory.
a. Implicit inclusion. In its 1986 Policy Statement, EPA stated
that intergeneric microorganisms were the only microorganisms that
would not be implicitly included on the Inventory. As discussed in Unit
I.C. of this preamble, EPA will continue to use the 1986 Policy
Statement interpretation for this rulemaking.
b. Explicit listing. A microorganism is not new, if it is
explicitly listed or implicitly included on the Inventory.
Microorganisms are placed on the Inventory if they have been previously
manufactured in the United States for general commercial use. EPA
explicitly lists microorganisms that it has previously reviewed, after
it is informed that production has begun through receipt of a Notice of
Commencement of Manufacture (NOC) (see Sec. 725.190). If a
microorganism is not considered to be implicitly included on the
Inventory, the public Inventory needs to be consulted to determine
whether the microorganism is explicitly listed. Microorganisms may also
be explicitly listed but treated as confidential and not placed on the
public Inventory.
c. SNUR listing. After persons determine that their microorganisms
are included on the Inventory, they must then check to see if the
microorganisms are subject to a SNUR. Where appropriate, microorganisms
subject to SNURs will be identified, both on the Inventory and in
Subpart M of part 725. The SNUR process is discussed in Unit IV.C. of
this preamble.
2. Consulting EPA when microorganism identity or use is
confidential or uncertain. Specific situations arise under these rules
when persons would need to consult listings of microorganisms to
determine whether a particular microorganism, or use of a
microorganism, is subject to reporting. These listings include the
Inventory; Subpart M of part 725, which lists significant new use
rules; and Sec. 725.239, which lists certain microorganisms exempt from
R&D reporting under part 725. The listings are explained in the text of
the regulation.
There would be two specific circumstances under which it may not be
possible to determine whether a particular microorganism is listed.
First, the actual identity or use may be claimed confidential by a
person who originally manufactured or processed the microorganism. In
this case, a so-called generic name or use would appear on the public
Inventory, and the actual identity or use would be on a confidential
listing not available to the public. Unit IV.D. on Confidential
Business Information (CBI) explains the generic name and use. The
second circumstance would be that a non-confidential identity of a
microorganism may not be precise enough for a person to determine
whether it describes a particular microorganism that could be subject
to reporting. This circumstance may arise because of the imprecision of
scientific nomenclature in biology, particularly in microbiology, or
because similarities in modified genetic material may raise questions
of equivalency (see Unit IV.B.).
To assist persons in determining their reporting obligations, EPA
has established a procedure whereby a person may file a submission
establishing a bona fide intent to manufacture or process a
microorganism and request that the Agency determine whether that
microorganism is on the applicable listing. EPA's goal is to respond in
30 days to the request, informing the requestor whether there is an
obligation to report under these regulations (see Sec. 725.15). This
procedure allows EPA to ensure appropriate reporting while maintaining
the confidentiality of legitimate trade secrets. This is a well-
established procedure in the Agency's current regulations on TSCA
section 5 reporting (see Secs. 720.25 and 721.11). This preamble will
note when this process, known as a ``bona fide,'' applies.
B. General Administrative Procedures
After submitters determine that they have a microorganism subject
to TSCA section 5, they must determine what type of submission will
satisfy their reporting obligations. The first decision is whether the
microorganism will be used for R&D or general commercial use. The
specifics of the submission and review processes for general commercial
use and for R&D are covered in Units II.C. and II.D. of this preamble,
respectively. However, some administrative procedures apply generally
to all microorganism submissions. Therefore, general administrative
procedures are discussed in this Unit.
Subpart B of part 725 contains administrative procedures generally
applicable to all submissions. Most of these are rather mechanical,
such as general recordkeeping requirements, procedures for determining
whether submissions are complete and properly filed, how to determine
when the Agency will begin the review period designated for a
particular submission, and under what circumstances the Agency or the
submitter may suspend, extend, or terminate a review. The more
important administrative procedures are discussed in this Unit.
1. Prenotice consultation. EPA recommends that potential submitters
begin discussions with EPA staff early in the submission planning
process to identify any special data requests and preliminary concerns
that may be associated with the microorganism. This may save
significant time later in the review process. Any meetings and relevant
written communications may be claimed confidential. Persons who are
unsure as to whether their microorganisms are subject to any of the
requirements of part 725 should consult with EPA before preparing any
submission.
With reference to R&D, EPA recognizes that research proceeds
through various stages. Potential submitters may find it advantageous
to begin discussions with EPA as early as the grant proposal stage,
even though they would not be required to file a submission under part
725 until the latter stages of their research program. Early
consultation with the Agency could assist submitters in the planning
stages of their research program in addition to providing a smoother
submission and review process.
2. Submission process. The general requirements pertaining to the
submission process are found at Secs. 725.25 through 725.36.
a. Preparing submissions. The data to be included in submissions
for microorganisms would be different from those for traditional
chemicals, because microorganisms may pose different risks than those
posed by traditional chemicals. To assist persons preparing submissions
under this proposed rule, EPA has developed a special guidance document
entitled ``Points to Consider in the Preparation and Submission of TSCA
Notifications for Microorganisms.'' At this time, a special form has
not been developed for microorganism submissions. Therefore, persons
preparing microorganism submissions should follow the format outlined
in the guidance document. This document is available from the
Environmental Assistance Division (see the address listed under the FOR
FURTHER INFORMATION CONTACT Unit).
The regulatory text describes the type of information that is
relevant for each specific type of submission. Submitters should submit
all reasonably ascertainable information which they believe will assist
EPA in evaluating the microorganisms, including information not
specifically listed that submitters believe will be useful for EPA's
risk assessment. When information listed in the regulatory text is not
submitted, a brief explanation of why such information is not available
or not applicable should be included. Prenotice consultation may assist
in identifying specific information appropriate for a submission.
b. Incomplete submissions. After an initial evaluation, EPA may
determine that a submission is incomplete and that the review period
cannot begin (see Sec. 725.33 of the regulatory text). If EPA finds the
submission incomplete, EPA will notify the submitter within 30 days of
receipt of the submission and will provide the submitter with an
opportunity to provide additional information. If the submitter
promptly provides additional information sufficient to evaluate the
effects of the microorganism, the evaluation will not be delayed beyond
time for a reasonable consideration of the new information. Otherwise,
EPA may declare the submission incomplete and the review period will
not begin until EPA receives the necessary information.
3. Review process. The requirements pertaining generally to the
review process are found at proposed Secs. 725.40 through 725.60.
a. Public involvement. EPA is aware that there is considerable
public interest in the review of submissions involving new
microorganisms and is committed to keeping the process as open as
possible. Following receipt of a submission, EPA is required by TSCA to
issue a notice in the Federal Register describing the submission (see
Sec. 725.40 of the regulatory text). The Federal Register notice would
include nonconfidential information on such items as the identity of
the microorganism, the type of use, occupational exposure, production
volume, a summary of test data included in the submission, and the
submitter's identity. If microorganism identity and use are claimed
confidential, EPA includes generic descriptions of this information in
the Federal Register notice. Unit IV.D. of this preamble discusses
confidentiality and generic descriptions. EPA would maintain a
nonconfidential copy of the submission in the TSCA Nonconfidential
Information Center for public inspection. The public will have an
opportunity to comment on submissions received by EPA. The length of
the comment period may be affected by the need to hold a meeting of
experts to address a particular submission, or to consider novel
scientific issues raised by the submission.
b. State coordination. EPA has developed comprehensive procedures
to coordinate reviews of submissions and to share scientific
information to the fullest extent with appropriate State and local
authorities. For example, under EPA's current procedures for review of
field tests under the 1986 Policy Statement, within the first week of
receipt of a submission, an EPA review coordinator contacts by
telephone the appropriate regulatory agencies in the State(s) where the
test will be conducted to inform them of the submission. If requested,
a nonconfidential copy of the submission is mailed to the State. If a
site visit is to be conducted, EPA staff contacts State and EPA
regional personnel early in the review period to begin coordination of
the site visit. Nonconfidential reports, assessments, and public
comments added to the Public Docket are routinely made available to
State personnel upon request. In addition, State personnel receive a
copy of EPA's draft risk assessment, and comments and concerns raised
by the State(s) are given careful attention in the risk assessment. At
the conclusion of the review period, State personnel receive a copy of
any document which addresses the conditions under which the field test
can be performed.
EPA is also requiring that persons who are preparing submissions
for R&D activities provide evidence of having notified appropriate
State authorities (see Sec. 725.255 of the regulatory text). Submission
of copies of any correspondence with State authorities concerning the
proposed field trial, for example, would satisfy this requirement. EPA
also strongly encourages such submitters to inform communities located
near potential test sites of their plans to introduce microorganisms
into the environment.
c. Use of experts. In performing assessments, EPA intends to
supplement its staff expertise as necessary by using experts from other
government agencies, academia, and other independent sources. EPA
assessments may be reviewed by a subcommittee, composed of scientists
with relevant expertise, of EPA's Biotechnology Science Advisory
Committee (BSAC) at a public meeting. Certain portions of the meetings
may be closed to discuss confidential business information (CBI). EPA
will consider all BSAC Subcommittee recommendations in its final
decisions. Procedures have been developed to ensure that experts
contributing to EPA's biotechnology reviews will not have conflicts of
interest.
d. Changes to the review process. The review period starts on the
date EPA determines the submission is complete and runs for a period of
time specified for each submission type. A submitter may voluntarily
withdraw a submission at any time, or suspend the review period for a
specified period of time. Suspension of the review period may be
beneficial when questions that arise during the notice review period
require additional time to address. For good cause, EPA may extend the
review period up to a total of the length of time specified for each
type of submission.
4. Recordkeeping and compliance. The requirements for
recordkeeping, compliance, and inspections are found at Secs. 725.65,
725.70, and 725.75, respectively. In addition to recordkeeping
requirements generally applicable to all submissions, EPA is proposing
recordkeeping requirements specific to each submission type. For
certain exemptions from full reporting under section 5, the
recordkeeping requirements are a key part of compliance with the
exemption. Compliance and inspection requirements are the same as those
for traditional chemicals.
5. Petitions to exempt new microorganisms. Provisions for
applications to request exemptions for new microorganisms from the
requirements of all or part of part 725 are found at Sec. 725.67.
C. Reporting General Commercial Use of TSCA Microorganisms
This Unit discusses who is subject to microbial commercial activity
notice (MCAN) reporting, the MCAN submission and review process, and
exemptions from MCAN reporting for general commercial use.
1. Determining whether MCAN reporting is required. Subpart D of
part 725 would require, with some exceptions, submission of a MCAN by
persons who intend to manufacture or import new microorganisms, and by
persons who intend to manufacture, import, or process microorganisms
for a significant new use. A MCAN must be submitted 90 days before
manufacture, import, or processing of the microorganism for commercial
purposes. Because EPA has a separate, less burdensome, screening
process for R&D involving microorganisms (see Unit II.D. of this
preamble), the Agency expects that, in general, the MCAN will be
submitted only for microorganisms for general commercial use.
2. MCAN submission and review process--a. MCAN submission process.
The purpose of EPA's review of MCANs would be similar to EPA's purpose
in reviewing PMNs and SNUNs submitted for traditional chemical
substances. The purpose of a MCAN would be to provide EPA with
information necessary to identify and list a microorganism on the TSCA
Inventory (if the microorganism is new) and to determine whether the
microorganism would pose an unreasonable risk to human health or the
environment. EPA must conduct a review that considers all the
reasonably ascertainable information on potential human health and
environmental effects of a microorganism. The information to be
included in the MCAN is listed in Secs. 725.155 and 725.160 of subpart
D. Submitters must develop a MCAN that describes the characteristics
and construction of the new microorganism as well as describing
conditions of manufacture and use. In addition, submitters must
reference any published literature on the microorganism and its
parental strains and submit available data from laboratory, greenhouse
studies, and/or R&D field tests using the microorganism.
b. MCAN review process. All reviews of microorganisms will follow
established administrative steps that are the same for all chemical
substances subject to 90-day review. For good cause, EPA may extend the
initial review period by an additional 90 days, for a total of 180
days. During this time the microorganism cannot be manufactured or
processed for commercial purposes.
c. Regulatory decision. EPA may reach one of three decisions during
the review period based on a balancing of the risks and benefits
presented by the microorganism: There is sufficient information to
determine that the risks will not be unreasonable; there is sufficient
information to determine that the risks are unreasonable; or there is
insufficient information to make a reasoned evaluation of risk, and the
substance may present an unreasonable risk or there may be significant
or substantial human or environmental exposure to it.
Unless EPA notifies the submitter to the contrary, the submitter
may begin to manufacture and use the microorganism at the end of the
90-day period. However, if the information available is insufficient to
reasonably evaluate the risk and the substance may present an
unreasonable risk, EPA may issue an order under TSCA section 5(e) to
limit or prohibit the manufacture, processing, distribution in
commerce, use, or disposal of the microorganism. In the past, EPA has
found it useful to negotiate with submitters to develop consent orders,
sparing both the submitter and EPA the legal proceedings that may be
involved in a unilaterally issued order. Under a consent order, the
submitter generally agrees to develop additional information or to
accept certain restrictions in return for permission to proceed with
its plans to manufacture or import the substance.
In the situation where EPA decides that risks will be unreasonable,
it may use TSCA section 5(f) to require measures to reduce risks to an
acceptable level as a condition of manufacture and use. Alternatively,
EPA may prohibit manufacture or use, if there are no measures available
or practicable to sufficiently reduce the risk.
3. Exemptions from MCAN reporting. Persons intending to manufacture
new microorganisms for general commercial use may not have to submit a
MCAN prior to commencing manufacture, if the microorganisms they intend
to use qualify for exemptions from MCAN reporting. This unit discusses
one exemption developed for traditional chemicals that will not be
applied to microorganisms and two exemptions that are applicable to
microorganisms.
a. Low volume exemption. EPA has previously promulgated rules
providing for an exemption from the notification requirements of
section 5 of TSCA for new chemical substances produced for general
commercial use in volumes less than 1,000 kilograms per year (see 40
CFR 723.50). This exemption requires applicants to submit a notice to
EPA 21 days before manufacture begins to provide the Agency an
opportunity to review the chemical. EPA believes that this exemption is
inappropriate for microorganisms, which have the ability to reproduce,
disseminate, and transfer genetic material. EPA is therefore proposing
to amend Sec. 723.50 to state that the exemption provisions of that
section do not apply to microorganisms.
b. Test marketing exemption. Test marketing activities usually
involve limited sale or distribution of a substance within a
predetermined period of time to determine its competitive value when
its market is uncertain. EPA is required by TSCA section 5(h)(6) to
grant or deny the test marketing exemption (TME) no later than 45 days
after receipt of an application. Subpart F of part 725 proposes the
requirements for obtaining a TME. These requirements are adopted
verbatim from Sec. 720.38, the Agency regulations that currently apply
to all chemicals substances.
In general, EPA suggests that manufacturers who intend to test
market new microorganisms file a MCAN rather than a request for a TME.
However, there may be situations in which this exemption may be
appropriate, such as for microorganisms which were previously reviewed
by EPA at the R&D stage. EPA encourages anyone who is considering
requesting a TME for a new microorganism to begin prenotice
consultation as early as possible, so that EPA can determine if it
would have sufficient information to determine that the test marketing
activities would not present an unreasonable risk.
c. Tiered exemption for general commercial use. Under TSCA section
5(h)(4), EPA is proposing to exempt from MCAN requirements certain new
microorganisms manufactured for general commercial use which it has
determined will not present an unreasonable risk. Subpart G of part 725
contains the conditions for this exemption, which consists of two
tiers, each based on certain criteria discussed below. The rationale
for this exemption appears in Unit III.C.7. of this preamble.
Microorganisms produced under this exemption would not be listed on the
Inventory.
(i) Tier I. Manufacturers meeting Tier I requirements will be
completely exempt from review by EPA. They would submit a one-time
certification statement to EPA 30 days prior to the first use of a
microorganism eligible for a Tier I exemption. The conditions for this
exemption are listed at Sec. 725.424. The statement must include
information identifying the manufacturer or importer, the location of
the facility involved, and a statement certifying that the manufacturer
complies with all the criteria required for the Tier I exemption.
Information in the statement may be claimed confidential. A
certification would be required for the first use of an eligible
recipient microorganism at a specific facility. Subsequent uses of the
same recipient microorganism at the same facility would not require
additional certification, so long as the manufacturer complied with the
other Tier I exemption conditions.
(ii) Tier II. Manufacturers meeting the requirements at proposed
Sec. 725.428 may submit an exemption request to EPA 45 days prior to
use of the microorganisms, if they believe that containment conditions
other than those listed at proposed Sec. 725.422 would still allow the
requirements of the exemption to be met (see Sec. 725.455 of the
regulatory text). Information included in such a submission may be
claimed confidential. Submitters must certify in the request that they
have complied with the requirements. EPA would approve or deny an
exemption request within 45 days and could impose restrictions to
ensure that the microorganisms would not present an unreasonable risk
(see Sec. 725.470 of the regulatory text).
(iii) Criteria for the exemption. Three conditions are placed on
the Tier I and Tier II exemptions. The recipient microorganisms must be
listed at proposed Sec. 725.420, the introduced genetic material must
meet certain requirements, and performance-based criteria for
containment and inactivation of the new microorganisms are to be used.
(A) Recipient microorganisms. EPA is proposing that new
microorganisms certified to be developed using a recipient species or
strain listed at proposed Sec. 725.420 would qualify for the tiered
exemption.
(B) Introduced genetic material. The introduced genetic material
used to modify the recipient microorganisms must be well characterized,
limited in size to the genetic material required to perform the
intended function, and poorly mobilizable (see Sec. 725.421 of the
regulatory text). Further explanation of these terms appears in Unit
III.C.7. of this preamble. In addition, genetic material which encodes
for all or part of the toxins listed in proposed Sec. 725.421(d) may
not be used to modify any recipient microorganism.
(C) Containment and inactivation. EPA is also proposing
performance-based criteria for limiting exposures. These criteria would
have to be used for the Tier I exemption, because EPA would not review
these activities prior to production. For the Tier II exemption,
because the containment and inactivation controls would be reviewed in
the exemption request, the criteria would serve as guidance for
submitters. Proposed Sec. 725.422 lists the criteria for containment
and inactivation at a facility.
(iv) Exemption applications. Using the provisions in proposed
Sec. 725.67, individuals may submit an application under section
5(h)(4) requesting that a recipient microorganism be added to the
exempt list. Submitters may request an exemption with different
conditions. EPA would evaluate the request using appropriate procedures
under section 5(h)(4).
D. Reporting R&D Activities for TSCA Microorganisms
This Unit discusses EPA's proposal for which microorganisms are
subject to R&D reporting and recordkeeping, exemptions from R&D
reporting, and the TSCA experimental release application (TERA)
submission and review process.
1. Overview of considerations for determining whether a researcher
has TSCA section 5 obligations for R&D activities. Persons planning to
conduct R&D activities involving new microorganisms subject to TSCA may
be subject to these rules. While any researcher may submit a complete
MCAN as required for general commercial use, EPA is proposing a number
of exemptions from MCAN reporting that reduce researchers' reporting
obligations under TSCA section 5. All R&D activities are eligible for
reporting using the TERA process which is discussed below. However, EPA
expects that the TERA will be used primarily for environmental
experiments. Laboratory and other research in contained structures
would more likely comply with certain recordkeeping requirements
provided under TSCA section 5(h)(3) in the rule. Finally, certain
research may be exempt from TSCA section 5, because EPA has determined
review is unnecessary altogether or it is appropriate to defer in
whole, or in part, to another Federal agency.
The series of considerations to be used to determine TSCA section 5
obligations for R&D activities is displayed in chart form in Figure 1
below. The following paragraphs summarize the steps on Figure 1.
The first three steps list the issues that must be addressed for
determining if any substance is subject to TSCA section 5 reporting,
whether for general commercial use or for R&D activities. The
subsequent steps are employed to determine R&D obligations. Determining
whether an R&D activity is subject to TSCA jurisdiction and whether the
microorganism is intended for commercial purposes are discussed below
in Units II.D.2.a. and 2.b., respectively. Determining whether a
microorganism is ``new'' for the purposes of TSCA section 5 is
discussed in Unit I.C. of this preamble.
If researchers have determined that their R&D activities are
subject to TSCA jurisdiction, are intended for commercial purposes, and
involve new microorganisms, their R&D activities will be subject to
some obligations under TSCA section 5. Researchers would then proceed
through the remainder of the questions to determine their reporting
status. They would first determine whether their R&D activities are
eligible for the contained structures exemption. This determination is
discussed below in Unit II.D.2.c.
The next question deals with other agencies. An R&D activity that
is eligible for the contained structures exemption may also be subject
to the authority of another Federal agency. Overlapping jurisdiction
for R&D conducted in contained structures is discussed below in Unit
II.D.2.d.
If the R&D activity does not qualify for the contained structures
exemption, TERA reporting would next need to be considered. However,
EPA is also proposing in this rulemaking a category of specific
microorganisms that are exempt from TERA reporting. Thus, researchers
who are not eligible for the contained structures exemption and/or for
deferral to another agency may qualify for a specific TERA exemption.
The determination of whether the research qualifies for a TERA
exemption is discussed below in Unit II.D.2.e.
Figure 1 shows the four distinct types of TSCA section 5
obligations existing for R&D activities. The reporting requirements for
each of these obligations are discussed below in Units II.D.3. and 4.
The corresponding paragraphs are noted on the following Figure 1.
TP01SE94.000
2. Specifics for determining eligibility for R&D exemptions. The
five points which researchers must consider in order to determine their
TSCA section 5 obligations for R&D are discussed in this paragraph.
a. Determination that the R&D activity is subject to TSCA
jurisdiction. Statutory jurisdiction is discussed in Unit I.C. of this
preamble. As noted in that Unit, uses of some microorganisms are
specifically excluded from TSCA section 5, because they are subject to
other statutes. Uses that are not specifically excluded are subject to
TSCA. When developing the initial TSCA Inventory, EPA indicated that
undifferentiated uses of chemical substances would be subject to TSCA
(42 FR 64585, December 23, 1977). In the 1986 Policy Statement, EPA
stated that unless the uses were explicitly excluded by TSCA, ``all
microorganisms produced for environmental, industrial, or consumer uses
are potentially regulable under TSCA'' (51 FR 23324, June 26, 1986).
Thus, 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. This would include microorganisms in early
stages of research, where the researchers have not determined a
specific commercial application of the microorganism. As noted in Unit
II.B. of this preamble, researchers who are uncertain of the status of
their microorganism, for any reason, should consult EPA regarding their
TSCA section 5 obligations.
b. Determination that the R&D activity is intended for commercial
purposes. TSCA section 5 covers only uses of new microorganisms for
commercial purposes. EPA discusses its interpretation of commercial R&D
in Unit III.A. of this preamble. The Agency is proposing three
alternative interpretations of commercial purposes. Depending on public
reaction to the alternative interpretations discussed in this proposal,
the interpretation of commercial R&D could differ from one R&D activity
to another in a final rule, if public comment supports different
interpretations for different types of R&D activities.
c. Determination that the R&D activity is eligible for the
contained structures exemption. This exemption would most likely apply
to research performed in contained structures such as pilot
fermentation plants, greenhouses, laboratories, and certain bioreactors
used for waste treatment. The term ``structure'' is defined in proposed
Sec. 725.3. Research involving intentional testing of microorganisms in
the environment would not be eligible for this exemption. Requirements
for the exemption are in section 3 of this Unit. The rationale for this
exemption is discussed in Unit III.B. of this preamble.
d. Determination that oversight of the R&D activity is also subject
to the authority of another Federal agency. Some R&D activities may be
subject to the authority of another Federal agency in addition to EPA.
Where there is overlapping jurisdiction for R&D activities that are
eligible for the contained structures exemption, EPA proposes to defer
to the other Federal agency which has authority for oversight over such
activities. This would apply to researchers who are receiving funding
from the other Federal agency, which requires that researchers comply
with the ``NIH Guidelines for Research Involving Recombinant DNA
Molecules'' (``NIH Guidelines'') in order to receive funding.
Researchers who are voluntarily complying with the NIH Guidelines but
are not actually receiving funding from a Federal agency would not be
eligible for the deferral.
e. Determination that specific microorganisms are exempt from TERA
reporting. EPA is proposing exemptions from TERA reporting for certain
new microorganisms derived from the microorganisms Bradyrhizobium
japonicum and Rhizobium meliloti. R&D involving these microorganisms
performed in accordance with specified conditions would be exempt from
review. Additional microorganisms may be exempted by rule under section
5(h)(4), as EPA gains familiarity with them. Unit III.C.5. of this
preamble discusses the rationale for this exemption.
3. Requirements necessary for eligibility for exemptions from TERA
reporting. Once researchers have determined which exemptions their R&D
activities are eligible for, they must determine their specific TSCA
section 5 obligations. Proposed Secs. 725.232 through 725.239 specify
the requirements for each of the exemptions from TERA reporting.
a. The contained structures exemption--(i) R&D subject to another
Federal agency. R&D activities which are eligible for the contained
structures exemption (see Sec. 725.234(a) and (c) of the regulatory
text) but are also subject to the oversight of another Federal agency
will be exempt from the requirements of TSCA section 5. If researchers
comply with the other agency's requirements, there will be no EPA-
specific requirements (see Sec. 725.232 of the regulatory text).
(ii) R&D not subject to another Federal agency. This document
proposes that R&D eligible for the contained structures exemption but
not subject to another Federal agency must be conducted in accordance
with proposed Secs. 725.234 (containment and recordkeeping) and 725.235
(employee notification). Although researchers that comply with these
provisions are not required to report to EPA under TSCA section 5, the
recordkeeping and employee notification requirements would apply and
would be enforceable by EPA.
There are two types of standards in Secs. 725.234 and 725.235. The
employee notification standards of Sec. 725.235 are taken directly from
current regulations in Secs. 720.36 and 721.47, and are the same as
those for traditional chemical substances. Section 725.234 contains
general research standards but adds some provisions that apply
specifically to microorganisms. However, these additional provisions
are minor changes to EPA's current requirements for the research
exemption, and these provisions should be standard practices for
research activities involving microorganisms.
Specifically, the small quantities exemption for traditional
chemical substances requires research to be conducted by, or directly
under the supervision of, a technically qualified individual (TQI).
This is a requirement under EPA's current regulations at Secs. 720.36
and 721.47. Section 725.234 applies the same requirement to
microorganisms eligible for the contained structures exemption.
Section 725.234 states that the TQI must select appropriate
measures to control release of the research microorganism, write a
brief description of the reasons for choosing the measures and ensure
maintenance of records to document routine use of the selected
controls. In addition, the choice of control measures must be certified
by an authorized official of the institution at which the research is
conducted. Finally, EPA may request that the records be sent to EPA for
review. Subsequent to such review, EPA may in some circumstances offer
recommendations to modify control or documentation measures. In what
EPA anticipates would be rare occurrences, EPA might order the
researcher to modify controls or documentation measures. Failure to
comply with such an order would result in loss of eligibility for the
exemption for the specific R&D activity.
For those researchers who are voluntarily complying with, but are
not subject to, the NIH Guidelines, the requirements of the contained
structures exemption could be met by having the principal investigators
serve as the TQIs (see Sec. 725.234(b) of the regulatory text) and keep
records indicating that they abide by the NIH Guidelines.
b. Exemption from TERA reporting for specific microorganisms. In
order to be exempt from both TERA reporting and MCAN reporting, persons
using the exemptions for microorganisms listed in Sec. 725.239 must
comply with the general requirements for the exemption listed in
Sec. 725.238 as well as any specific requirements listed in
Sec. 725.239. Similar to its proposal for the tiered exemption for
general commercial use discussed in Unit II.C., EPA is proposing to
place restrictions on the recipient microorganisms, the introduced
genetic material, and the conditions of use (see Sec. 725.239 of the
regulatory text).
4. TERA submission and review process. EPA is proposing to
establish the TERA, which is an abbreviated notification process for
environmental testing of new microorganisms.
a. TERA submission process. Sections 725.255 and 725.260 detail
specific information that should be submitted with a TERA. The basic
microorganism identity information is the same as that for the MCAN.
Other information requested specifically addresses the proposed R&D
activity and therefore is not as extensive as the MCAN information.
b. TERA review process. EPA's goal is to review TERAs in 60 days
(see Sec. 725.270 of the regulatory text). For good cause, EPA could
extend the initial TERA review period by an additional 60 days, for a
total of 120 days (see Sec. 725.56 of the regulatory text). Due to the
small number of experiments that have been conducted and the
uncertainty concerning field tests that involve new microorganisms, EPA
expects that initial TERA reviews may take closer to 120 days. During
the prenotice consultation, EPA would estimate for the submitter
whether the review is likely to require closer to 120 days or 60 days.
Generally, EPA believes that approval of TERAs in 60 days or less
would be possible for field tests that are similar to previously
reviewed field tests (for example, use of the same or similar
microorganisms, modifications to a previous test, or change in
geographic conditions). When novel circumstances are presented in a
TERA, however, EPA may need to extend the review period in order to
complete its review. Specific examples of extension for good cause
would include the need for a subcommittee meeting of the Biotechnology
Science Advisory Committee to supplement Agency expertise or the need
to coordinate review with other Federal agencies. When EPA coordinates
the review of a microorganism with another Federal agency, the review
period would automatically be extended to the length of the other
agency's review, to allow the two agencies to coordinate reviews and
decisionmaking. TERA submitters may not proceed with their field trials
until EPA has provided written approval of the TERA submission. As soon
as EPA completes its review, however, researchers will be able to start
their test immediately upon notification from EPA.
c. Regulatory decision. EPA will approve a TERA if it determines
that the experiment(s) will not present an unreasonable risk to human
health or the environment. If the submission is approved, EPA may
negotiate with the submitter a TERA Agreement, which would be legally
binding on all parties and would set out any conditions governing the
conduct of the specific field trial (see Sec. 725.270 of the regulatory
text). The TERA Agreement could include provisions for maintaining
restrictions on the use of the test site after the completion of the
test. This may require the submitter to make appropriate arrangements
with the owner of the test site, in cases where the submitter does not
own the test site. If EPA concludes that the proposed R&D activity may
present an unreasonable risk of injury to human health or the
environment, EPA will deny the TERA and will provide reasons for the
denial in writing. Section 725.288 provides for revocation or
modification of TERA approvals following the receipt of additional
information.
5. Options for oversight of R&D activities--a. Range of options
possible. EPA's intent in offering a variety of alternatives for
oversight of R&D activities was to provide a flexible process which
tailored oversight to the level of risk. In developing TSCA section 5
obligations for R&D activities using new microorganisms, EPA looked at
a range of options. These fall on a continuum ranging from an option
which would exempt all R&D activities under a small quantities
exemption similar to the exemption for traditional chemicals to an
option which would require TERA reporting for all R&D activities,
including those conducted in laboratories and other contained
structures.
As discussed in Unit III.B. of this preamble, because
microorganisms can multiply and spread beyond the site of introduction,
EPA must redefine the small quantities definition applied to
traditional chemicals. EPA developed the TERA process, because it
believes that review of environmental uses of microorganisms should
begin during the R&D stage. At the same time, EPA does not believe that
all microorganisms used in all R&D activities should be subject to TERA
reporting. Neither of the extreme options seemed appropriate to EPA for
coverage of R&D, because they would not be tailored to potential risk.
Thus, EPA chose an intermediate approach.
In keeping with the goals of the Coordinated Framework, EPA has
included in its proposed option opportunities to address overlapping
jurisdiction with other Federal agencies. EPA has attempted to balance
the Coordinated Framework's goal to reduce duplicative oversight with
TSCA section 5's goal to screen for potential unreasonable risks. As
discussed in Unit III.B. of this preamble, in developing its
requirements for the contained structures exemption, EPA selected an
approach which recognized the diversity of microorganisms which would
be used in research and therefore left to the researcher the choice of
appropriate containment and inactivation controls. Additionally, in
order to keep the TERA process flexible, EPA has developed a provision
allowing microorganisms tested in the environment to be exempted from
TERA reporting as the Agency gains more familiarity with them.
EPA requests comments on its proposed option for R&D activities for
TSCA microorganisms. In particular, EPA would like to know whether
commenters feel that the flexibility provided by the various exemptions
available under the proposed option counterbalances the complexity of
the approach. The public may suggest other options along the continuum,
providing those options also meet the intent of TSCA and adequately
protect public health and the environment from unreasonable risks. In
addition to the proposed option, when EPA prepares its final rule, it
will consider the variety of options along the continuum discussed
above, as well as options suggested by the public.
b. Specific alternative for low risk field tests. EPA realizes that
there are a variety of possible options along the continuum discussed
above. Although EPA has decided that case-by-case review is important
for many microorganisms intentionally tested in the environment, EPA
recognizes that there will be low risk field tests that would not
require TERA review. For this reason, some have suggested an
alternative exemption for certain R&D releases. This alternative, which
is similar to the R&D contained structures exemption in that it would
be dependent on determinations made by a TQI, would apply to certain
low risk field tests and would be included with the exemptions which
are part of the proposal for coverage of R&D activities under TSCA
section 5. Like the proposed exemption for R&D in contained structures,
this alternative would contain requirements for documentation and
recordkeeping by a TQI and certification by an authorized company
official. It would also provide for EPA to inspect records and order
changes, if necessary.
Under this alternative, a company planning a small-scale field test
which meets the eligibility requirements for the exemption would have
the option of submitting a TERA for review by EPA or submitting a
notice with the determination that the field test qualified for the
exemption. The alternative includes a number of requirements which are
intended to minimize the likelihood of inconsistent determinations.
The TQI would be expected to make the determination that the new
microorganism was eligible for the exemption, based on the following:
(1) The test site must be 10 acres or less of land, (2) the parent
microorganism(s) must have a history of safe use, and (3) the
introduced genetic material must be limited in size, well-
characterized, free of certain nucleotide sequences, and poorly
mobilizable. Further explanation of the terms in (3) appears in Unit
III.C.7. of this preamble.
In determining that the parent microorganism has a history of safe
use, EPA would expect researchers to be able to classify taxonomically
the microorganism and to evaluate its relationship with closely related
microorganisms which may have a potential for adverse effects on human
health or the environment. Information on the potential for the
microorganism to cause adverse effects on human health and the
environment should be evaluated.
EPA recognizes that a determination that a microorganism has a
history of safe use involves a balancing of various factors. This
determination should be premised on the researcher's prediction of the
behavior of the microorganism based on experience with its use. The
more information the researcher has on the behavior of the
microorganism (for example, the ability to establish, compete, and
survive in the environment), the better the researcher can estimate the
safety of the field test. In conducting their risk assessment,
researchers should consider the scale, since the tests must be
conducted on 10 acres or less of land.
An additional requirement for this alternative exemption would be
that an official having authority to represent the organization (e.g.,
the Chief Executive Officer, the General Counsel) certifies that the
determination has been made by a TQI and is considered to be the
official position of the organization. The official would also be
required to state that the organization accepts full liability for all
potentially harmful consequences of the field test. To show that
relevant considerations had been evaluated, a TQI would be required to
prepare a written analysis to be kept in the company's records. These
records would be kept for 5 years from the date of the field test, with
EPA retaining the right to review the records upon request. In lieu of
a TQI, the analysis could be performed by a third party review group
with relevant scientific expertise (i.e., ecological expertise) as
exemplified by the Institutional Biosafety Committees (IBCs) described
in the NIH Guidelines.
Following the TQI's determination, the researcher would be required
to submit a short notice to EPA, providing the organization name and
address, a summary of the new microorganism and the proposed field
test, the name of the TQI, and the official certification, including
the liability statement. EPA would have 45 days to determine whether to
require submission of a TERA before the researcher could conduct the
planned field test.
EPA requests comments on this alternative approach for low risk
field tests. In particular, EPA would like to know whether there are
other criteria which would be appropriate for defining a category of
low risk small-scale field tests and what additional guidance would be
needed for researchers to utilize such an approach. The rationale for
this alternative exemption is discussed in Unit III.C. of this
preamble.
III. Rationale for Proposed Reporting Mechanisms
A. Research for Commercial Purposes
1. Introduction. TSCA section 5(i), while it limits all section 5
screening to activities for commercial purposes, has had little
practical effect on research using traditional chemicals, because of
the research exemption. However, because this proposed rule would place
more requirements on research with microorganisms than on research with
traditional chemicals, EPA believes it should provide its current view
on the applicability of the commercial purposes limitation to this
proposed rule.
As a preliminary matter, there is no difficulty in determining when
any chemical substance, including a microorganism, is being
manufactured or processed for a commercial purpose after the R&D stage.
It is clear when a PMN is required or when a MCAN would be required at
general commercial use.
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 research with these chemicals from section 5 screening.
However, as noted in Unit III.B. of this preamble, these rules propose
a small quantities definition for microorganisms; and this definition,
because it would recognize the ability of microorganisms to reproduce,
would differ from the definition for traditional chemicals. A
researcher utilizing microorganisms, therefore, may need to consider
what constitutes a commercial purpose.
Research involving microorganisms used in contained structures
would be considered ``small quantities solely for research and
development'' as defined at Sec. 725.3 of the regulatory text. Although
EPA expects the requirements for this contained structures exemption
simply to reflect common practices, a researcher may have to evaluate
whether research conducted in contained structures is commercial. The
contained structures exemption would not apply to field testing of
microorganisms because of the ability of living microorganisms to
reproduce and spread in the environment (see Unit III.B. of this
preamble). As a result researchers will, in all cases, need to decide
which environmental testing is commercial.
EPA wishes to emphasize that any coverage of research under this
proposed rule should not duplicate appropriate oversight by other
Federal authorities. As explained in Unit III.C.3. of this preamble,
contained research appropriately overseen by other Federal agencies
would be exempt from EPA oversight, because EPA believes such research
does not present an unreasonable risk. As a practical matter,
therefore, while testing conducted at institutions that do not normally
consider themselves commercial (academic and non-profit institutions)
could theoretically be commercial under interpretations discussed in
this Unit, EPA anticipates that other parts of these rules will exempt
much of the research from EPA oversight.
2. Public comments. During development of regulations on
biotechnology, EPA has received numerous public comments that differ
substantially on oversight of research. Of particular concern has been
the appropriateness of EPA review based on the status of an activity as
commercial rather than on its potential risk.
Comments argue that there is no reason to suspect any difference in
risk between commercial or noncommercial research. Thus, if a
university and a business release the same microorganism in similar
settings, both should be subject to oversight.
On the other hand, comments suggest there may be risk differences.
Some argue that a commercial enterprise is more likely to be careful
than a noncommercial institution due to concern for liability. Others
argue that academic researchers are more likely to be concerned with,
and aware of, the need to consider health and environmental safety
issues and that commercial entities may be willing to take shortcuts in
the interest of reducing costs.
Other comments complain that increased government regulations may
have a deleterious effect on academic research, because it may be more
difficult for pure research institutions to comply. Burdens that are
relatively minor for a business could be major for a university or an
individual researcher.
Comments have also indicated that a number of practical
difficulties increase the burden on research institutions. For example,
increasingly complex and intermingled financial arrangements in the
biotechnology field have emerged as universities seek funding from
businesses. These arrangements may result in universities conducting
product development for money or equipment donations from business.
Undue burdens to academic researchers can result from requirements that
research which is funded by a commercial entity be distinguished from
that funded by a noncommercial entity, particularly when a university
may pool its funds from various sources.
Finally, even though an academic research institution may engage in
product development for a business, the institution may not be engaging
in a commercial activity for its own benefit. For example, a university
may use income from a commercial entity to improve its teaching and its
ability to increase knowledge. Industry could be an important source of
income for upgrading equipment used for teaching.
The remainder of this Unit discusses EPA's view of the law and
policy and responds to these public comments.
3. EPA's view of the law as it applies to commercial activities at
noncommercial institutions. EPA wishes to make it clear that the
interpretations discussed in this Unit are consistent with
interpretations in current regulations. That is, a commercial activity
is one undertaken with the purpose of obtaining an immediate or
eventual commercial advantage. This is the common thread in
Sec. 720.3(r) which defines ``manufacture or import for commercial
purposes'' and Sec. 721.3 which defines ``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.''
All research conducted directly by a commercial entity is clearly
for commercial purposes, as was 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 product development, the activity is for
commercial purposes, regardless of the location. A business may not
avoid review by simply funding research at an academic institution.
In section 5, Congress distinguished between commercial and
noncommercial activities and, thus, expected them to be treated
differently. Although the statute has no definitive explanation as to
what this distinction means, it does not appear to have been risk-
based. EPA believes that Congress did not provide a definitive
explanation and therefore left to the Agency's discretion the balancing
of competing interests. TSCA section 2(b) states that it is the policy
of the United States that TSCA authority should be exercised so as not
to ``impede unduly or create unnecessary economic barriers to
technological innovation,'' while fulfilling the primary purpose of
assuring that innovation does not present unreasonable risks.
If EPA considers that section 5 provides a screening mechanism, as
opposed to a direct regulatory mechanism, EPA has an indication why the
commercial purposes limitation applies. Under other TSCA provisions,
EPA may regulate without regard to a commercial purposes limitation.
For example, the commercial purposes limitation does not apply to EPA's
authority under TSCA section 6 to prohibit or limit manufacture,
processing, or distribution in commerce of chemical substances if the
Agency finds that the particular activities present an unreasonable
risk.
By providing a commercial purposes limitation for EPA to cover
early phases of product development, Congress recognized the need for
EPA to balance the competing interests of fostering innovation and
protecting human health and the environment from unreasonable risk. In
balancing these interests, EPA could construe the commercial purposes
limitation to exclude relatively few activities during screening to
cover a broad range of risk possibilities. Therefore, the broadest
meaning of commercial purposes would miss hardly any research.
4. Alternative interpretations affecting which activities at
noncommercial institutions will be considered commercial. Any of the
three alternative interpretations of commercial purposes set forth
below, as well as any other interpretation that is suggested by public
comment and meets the intent of TSCA and adequately protects public
health and the environment from unreasonable risks, may be adopted by
the Agency in its final rule. Regardless of the alternative chosen, EPA
would encourage researchers to voluntarily consult with EPA to find out
if EPA considers their research to be commercial.
a. Indicia of commercial purposes. The usual way to interpret a
statutory term of art like ``commercial purposes'' would be to look for
indicia of commercial intent. This is what EPA does in its TSCA section
5 program for traditional chemicals. The Agency has not provided any
detailed public discussion of what these indicia may be for traditional
chemicals, but because the Agency will be reviewing R&D activities in
its biotechnology program, a discussion of these indicia for the
biotechnology program is appropriate.
While EPA may develop a general discussion, no exhaustive list of
commercial indicia can be developed a priori. If EPA adopts this
approach, the commercial indicia would apply to R&D in laboratories and
other contained structures, as well as to intentional testing in the
environment. Some environmental testing of new microorganisms would not
be screened, because it would not be for commercial purposes.
EPA acknowledges that noncommercial institutions may find it
difficult to trace funding for particular activities or to decide
whether an activity is commercial or not. However, EPA supports this
alternative, under the theory that the burdens of reporting to EPA are
costs of doing business for any organization that wants the benefits of
commercial financing. In addition, EPA believes that reporting at the
research stage under this proposed rule does not impose an unnecessary
burden on innovation and that the indicia described below would be
consistent with the intent of TSCA. There are two general categories of
commercial indicia for activities at nonprofit institutions; one
involves industry involvement, either directly or indirectly; the other
does not.
(i) Direct industry involvement. As noted above, any direct
industry involvement in an activity at a noncommercial institution is
for commercial purposes. Examples of direct commercial funding include
situations in which a commercial entity contracts directly with a
university, or 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.
(ii) Indirect industry involvement. Indirect benefits to the
commercial entity are not as clear. For example, a commercial entity
may give a gift to a research institution with no limits on the use of
the funds or research results. However, since the funds originated from
a commercial source, a commercial purpose may nonetheless exist. Other
indirect relationships between commercial and noncommercial entities
need to be considered. For example, a commercial entity may guarantee a
university bank loan for research, a faculty member associated with
biotechnology research may have a financial interest in a biotechnology
company, research may be conducted at a science park jointly owned by a
university and commercial enterprises.
(iii) No industry involvement. If there is no industry involvement,
EPA needs to look at the intent of the individual researcher or
institution. Entrepreneurial faculty members may obtain financial
rewards from their own inventions. Some may take out personal patents
or derive personal income. The university may benefit from the patents
or may sell products or services commercially, for example, to farmers.
Because products may be sold to consumers, EPA is inclined to consider
these activities commercial. However, if profits are used to support
research or improve teaching facilities, EPA may recognize a case for
considering the activity not to be commercial.
EPA could also consider activities supported by Federal or State
government to be commercial. Many of these government activities are
designed to foster economic benefits for particular groups, such as
farmers. Also, the government may support university centers for
technology transfer to industry. The issue may be philosophical,
regarding whether government economic activities benefit individuals or
the general welfare. EPA believes there are legitimate arguments for
either view.
Finally, EPA may consider all activities at a nonprofit institution
to be commercial if any activity is. Thus, if a company finances one
activity at the university, all of the university's research may be
considered commercial. If a university has an equity interest in a
biotechnology company or a faculty member is associated with a firm,
all the university's research activities may be considered commercial.
This interpretation is supported by the fact that commercial activities
free resources for noncommercial activities.
If EPA interprets all these situations strictly, for practical
purposes, almost all research could be commercial. EPA notes for
comment, however, not-for-profit institutions that obtain self-
generated funds through charitable or religious donations and
government grants for pure research to identify health or environmental
hazards. These situations may not be commercial under any
circumstances.
Regardless of the alternative chosen for environmental research,
EPA would base its interpretation of commercial purposes for research
qualifying for the contained structures exemption on the broad set of
indicia discussed under this first alternative, in light of its belief
that EPA requirements for contained commercial R&D are similar to
requirements placed on academic researchers by the NIH Guidelines. See
Unit III.B. of this preamble. Therefore, the second and third
alternatives would apply only to research which does not qualify for
the contained structures exemption.
b. All environmental research is commercial. Because of the ability
of microorganisms to reproduce, disseminate and spread and the features
of intentional testing in the environment, EPA believes it should
propose another interpretation to address such testing. Under this
interpretation, all intentional testing outside of contained structures
would be commercial. This interpretation would avoid the most
significant problem identified by comments, which is that there is no
real difference in risk between research conducted by industry and by
noncommercial entities.
As discussed more fully in Unit III.B. of this preamble,
microorganisms function differently than other chemical substances.
Because R&D involving the introduction of new microorganisms into the
environment involves greater uncertainty than R&D involving use of
microorganisms under contained conditions, EPA believes that a
different position is warranted for intentional testing of
microorganisms in the environment.
Because the TERA burden is structured to be minimal, EPA believes
reporting will not seriously restrict academic R&D. In fact, this
interpretation of commercial purposes in some respects could lessen the
burden on universities, because they will not have to separate their
industry funding from other funding that they may not consider
commercial.
While considering all environmental releases to be commercial may
seem contrary to the usual view, the actual status of funding for the
biotechnology industry supports this interpretation. Research
relationships in biotechnology are pervasive and take many forms.
According to an Office of Technology Assessment (OTA) report,
in recent years, the rapid proliferation of collaborations in
biological research, involving partnerships between universities,
industry and government, has greatly extended the frequency, scope
and visibility of such activities. Attempts to commercialize
biological techniques have occurred at an accelerated rate when
compared to other fields, involving a greater range of commercial
application than discoveries in most other disciplines. (Ref. 4,
page 13).
Even the United States government is involved, under the Technology
Transfer Act, in the commercialization of biotechnology, having
developed a technology transfer policy between universities and
industry with the goal of developing commercially useful products.
Nonprofit foundations also participate in activities for commercial
purposes, often to finance other nonprofit activities.
c. Rebuttable presumption of commercial activity. The same
arguments for the option that all environmental releases are commercial
support the rebuttable presumption option. The rebuttable presumption
is also supported by the need to distinguish commercial and
noncommercial activities under TSCA. The above discussion of commercial
indicia indicates the types of evidence that a researcher may present
to rebut the presumption. However, EPA believes that this option would
be burdensome to researchers, because it would require them to maintain
evidence concerning sources of funding for each environmental
experiment. EPA also believes that this approach would be less
protective of public health and the environment, because it does not
adequately address uncertainty about the behavior of new microorganisms
in the environment.
d. Voluntary consultation. EPA recognizes that regardless of the
interpretation of commercial purposes adopted for the final rule, it
will be difficult to apply any one interpretation in all cases. For
this reason, EPA would encourage persons who believe that they are
engaging in non-commercial R&D to voluntarily consult the Agency before
initiating testing of microorganisms that would be considered new if
used for commercial purposes.
B. Exemption for Research in Contained Structures
This Unit explains EPA's reasons for exempting from section 5
screening R&D activities performed under conditions that would minimize
the number of microorganisms emitted, or where appropriate prevent
emission of microorganisms from structures such as pilot fermentation
facilities, greenhouses, and laboratories. The R&D reporting process is
discussed in Unit II.D. of this preamble.
1. Background. The statutory authority for this exemption is TSCA
section 5(h)(3). 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.
Accordingly, proposed Sec. 725.3 provides that R&D activities involving
microorganisms would qualify for the section 5(h)(3) exemption when
these activities are conducted under conditions designed to meet
appropriate standards of containment and when employees are notified of
risks. Some R&D activities which are eligible for the contained
structures exemption may also be subject to the jurisdiction of another
Federal agency. In these cases, EPA proposes to defer to the authority
of the other Agency. The rationale for this proposed deferral is
discussed in Unit III.C.3. of this preamble.
2. Difficulties in ensuring that microorganisms used for R&D will
not increase beyond small quantities. EPA's current 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. To the extent a finite amount of a
traditional chemical released during an experiment may leave a test
site, it will only be diluted in the environment.
Living microorganisms are not, however, subject to these same
limitations. Microorganisms may reproduce and increase beyond the
number initially introduced, may establish in the environment (i.e.,
develop a self-sustaining population), and may spread beyond the test
site. Thus, what begins as a small, localized population of
microorganisms may become a large, widespread population. Even if
certain microorganisms do not exhibit the ability to reproduce,
increase in number, establish, and spread beyond the test site, they
may be capable of passing some of their traits to other microorganisms
in the environment. These other microorganisms may, in turn, multiply,
establish, spread and subsequently pass the acquired trait to other
microorganisms. This could result in widespread propagation of the
trait, and exposure of a number of different environments to novel
traits.
These abilities of living microorganisms render the general
definition of small quantities that applies well to traditional
chemicals invalid for microorganisms. If the definition developed for
traditional chemicals was applied to living microorganisms, EPA would
not review microorganisms until they were produced for general
commercial use. New microorganisms could be released, with no EPA
review, during R&D testing in the environment, perhaps numerous times,
and could become established and spread. This would defeat the purpose
of TSCA, which is designed to permit EPA to review chemical substances
before they become widely disseminated.
Consequently, a determination of what constitutes small quantities
for microorganisms requires that more factors be taken into
consideration than are considered for traditional chemicals. These
factors revolve around the probability that a microorganism will
establish itself in the environment. Establishment is a key
consideration, because unless a microorganism establishes, any effects
it might have would probably be spatially and temporally limited.
Several factors influence whether a microorganism will be able to
establish itself. These include the numbers of microorganisms involved,
the frequency with which they are applied to the area, the method of
application, the characteristics of the microorganism, the
physiological condition of the microorganism at the time of
application, and the characteristics and condition of the receiving
environment.
Case histories of both disease epidemics and invasions of higher
organisms suggest that the number of organisms present in the inoculum
directly influences whether the introduction yields a self-sustaining
population (Ref. 5). Experience with microorganisms used in biocontrol
(i.e., purposeful use of microorganisms as antagonists to reduce the
disease-producing ability of plant pathogens) has shown that success in
some instances can be enhanced if a large number of the biocontrol
microorganism is introduced (Ref. 6).
It can be inferred from this information that the number of
organisms, both with regard to the density of the inoculum and the
geographic range over which it is introduced (Refs. 7 and 8), is
related to probability of establishment. Several hypotheses on why this
may be so can be offered. In some cases, mortality in the introduced
population can be overcome if the inoculum contains a large number of
individuals. In other situations, a large inoculum population may
provide sufficient genetic variation that individuals that can tolerate
or prosper in the environment of introduction will be within the
inoculum (Refs. 9 and 10). A biocontrol strategy that relies on the
inoculum containing large numbers of microorganisms is thought to be
successful because the introduced microorganisms may by sheer numbers
have an advantage in reaching and filling available suitable
microhabitats, availability of suitable habitat being a limiting factor
for any population of organisms.
The frequency with which organisms are released to an environment
also affects whether an organism can establish. Frequent releases
increase the likelihood that the microorganism will find sites
favorable for establishment by increasing the total number of
microorganisms placed in the environment and by increasing the
probability that a microorganism will be introduced during a time
favorable for establishment. This latter probability is related to
factors such as the variations in temperature, moisture, light, and
biota observed with seasonality. In other words, conditions favorable
for establishment may exist at some period of time and not at others,
and frequent application increases the probability that some
individuals will be at the right place at the right time.
3. Regulatory conditions to prevent microorganisms used for R&D
from increasing beyond small quantities. EPA's proposed standards at
Secs. 725.234 (containment and recordkeeping) and 725.235 (employee
notification) are designed to reduce the probability of establishment
by reducing the number and frequency of viable microorganisms emitted
from a facility. The reduced probability of establishment increases the
probability that a microorganism will remain a small quantity.
EPA is proposing performance-based standards for this exemption.
EPA's approach relies on the experience and judgement of the TQI, and
EPA will not generally substitute its own judgement for that of the
TQI. The approach recognizes that many different kinds of
microorganisms displaying a wide range of characteristics could
potentially be used in research, and that for certain microorganisms,
emission of only a few viable individuals could cause an effect, while
emission of large quantities of viable microorganisms of another type
would not. It also recognizes that the type of controls (e.g.,
procedural, mechanical, and/or engineering) appropriate for one
microorganism might have limited relevance to other microorganisms. EPA
expects that the TQI will be cognizant of these factors when selecting
containment and inactivation controls appropriate to the
microorganism(s) being utilized.
EPA does not believe the documentation requirements proposed for
this exemption will be overly burdensome. EPA believes that for most
cases, laboratory notebooks normally kept in the course of research
will contain most of the information required by this proposal. Control
measures selected could be indicated by reference to existing standards
(e.g., one of the containment levels described in the NIH Guidelines).
The TQI would simply record the reasons for choosing particular
measures. With regard to the requirement that records document use of
the selected controls, EPA is relying on the TQI to prepare and retain
the appropriate degree of documentation. The amount of documentation
would be correlated with the characteristics of the research
microorganism and standard practices employed to address risk. Thus,
documentation could range from general documentation of routine
standard operating procedures, to specific notations in laboratory
notebooks, to daily log entries for microorganisms that present the
greatest risk concerns. If the NIH Guidelines are used as guidance, the
TQI's notebook should indicate the level of containment recommended by
the Guidelines and that this guidance was selected and used. EPA
believes that persons following the NIH Guidelines would keep adequate
records as part of normal procedures for informing their Institutional
Biosafety Committee of the contained research.
With respect to the certification requirement, many if not most
research institutions have Institutional Biosafety Committees (IBCs) as
required by the NIH Guidelines, or committees fulfilling a similar
role. These committees are charged with assessing the containment
selected by the investigator. EPA recognizes the value of this NIH
system and would like to make its requirements consistent to the extent
possible with such existing systems. The Agency also encourages the
active use of such committees.
The provision which indicates that EPA may request these records be
sent to EPA for review (see Sec. 725.234(d)(3) of the regulatory text)
is a restatement of the authority EPA has under TSCA section 11 to
request and review information. It is also similar to provisions used
by EPA in other exemptions. In the three exemptions from PMN reporting
under part 723 that currently exist for traditional chemicals, one of
the conditions for eligibility for the exemptions gives EPA access to
the records demonstrating eligibility for the exemptions. EPA can
require a company to produce the records upon EPA's written request.
EPA does not plan to routinely review such records, although it may
choose periodically to select some records for review. Should the
institution or researcher receive a request for records review, the
status of the research as exempt would not a priori be affected.
Technical staff with experience reviewing TERA and MCAN submissions
would examine the records. This provision allows EPA and the researcher
to discuss what constitutes appropriate control measures and
appropriate implementation and use. Under this provision, EPA may, upon
review of the records, offer recommendations concerning what it
considers appropriate control measures for the specific microorganisms
used in the research. These recommendations would be non-binding. If
EPA determines, however, that the control measures selected and used
are so inadequate as to present an unreasonable risk, EPA can issue an
order directed at modifying the control measures it finds problematic.
Refusal to comply with an order would result in loss of eligibility for
the exemption for the research in question. The researcher would then
be subject to the notification requirements of TSCA section 5.
EPA's criteria at proposed Secs. 725.234 and 725.235 are designed
to reduce the probability of establishment by reducing the number of
viable microorganisms emitted from a facility. However, EPA's proposed
approach also takes into consideration factors such as the
physiological condition of the microorganisms and how this might affect
the ability of microorganisms to establish in the environment.
Microorganisms used in laboratory research are more likely to be
debilitated with regard to their ability to compete in the environment
against wild type relatives. Thus, they may be less likely to prevail
in the struggle in nature for limited resources. In general, incidental
releases of microorganisms from research facilities are less likely to
occur under conditions which favor the establishment of the
microorganism. Incidentally released microorganisms may be
physiologically debilitated by aerosolization or other process
procedures, and may be less likely to find an environment that favors
their survival and persistence than those microorganisms that are
specifically tested in an environment where they are intended to
survive, at least long enough to perform a specific function.
EPA recognizes that parts of the rationale offered for exempting
research conducted under the conditions set forth in proposed
Sec. 725.234 can be applied to some small-scale field tests involving
microorganisms. The rationale cannot, however, be applied to small
scale field tests as a class. Microorganisms intentionally tested in
the environment are more likely to be acclimated to the environment
into which they are introduced, be physiologically fit enough to be
competitive in that environment for a significant period of time, and
be placed in an area suitable for growth and persistence. Because of
the lessons learned with biocontrol microorganisms, researchers will
purposefully apply large enough numbers to ensure that the
microorganism persists long enough and competes well enough to perform
the function the researcher intends to study. In general, the
probability that these types of microorganisms, used under these
conditions, will establish is thus higher than the probability
associated with incidental emissions from facilities employing EPA's
proposed criteria.
4. Alternative reasons for the research exemption. An alternative
rationale would hold that the small quantities exemption in section
5(h)(3) does not apply to microorganisms as a class, because some
microorganisms, whether they are released through intentional testing
or incidental emission, can establish even though the initial inoculum
is very small. For some microorganisms, a single microorganism may be a
sufficient inoculum for establishment to occur. Thus, for
microorganisms as a class, there can be no concept of ``small
quantities'' similar to that envisioned for other chemicals.
EPA would find, however, that research conducted under the criteria
specified in Secs. 725.234 and 725.235 could be exempted under TSCA
section 5(h)(4). EPA's authority under TSCA Sec. 5(h)(4) is discussed
in Unit III.C. of this preamble. In situations where the EPA criteria
at Secs. 725.234 and 725.235 are followed, EPA believes that the
resulting reduction in the number of microorganisms emitted from R&D
facilities will reduce the probability that a microorganism will
establish in the environment. This reduced probability of establishment
leads directly to a reduction in risk. If a microorganism does not
establish, its ability to present risk is far less likely to be
expressed. If the microorganism is not able to establish, any adverse
effects that might be associated with that microorganism will probably
be spatially and temporally limited.
EPA recognizes that some research activities may present special
considerations; e.g., when the research utilizes microorganisms that
can successfully establish from a very small inoculum. In such cases,
incidental emission from the facility may have to be much more
stringently controlled to reduce risk. EPA believes that its
requirement that a technically qualified individual (TQI) select and
validate procedures appropriate to the microorganism addresses this
concern. That person should select, validate, and follow procedures
that would ensure that insufficient numbers of viable microorganisms
are emitted from the facility for establishment to occur.
EPA believes that any potential risk presented by incidental
releases from research facilities that might occur, even when its
criteria for reducing the number of microorganisms emitted from the
facility are followed, is outweighed by the benefits to society of
biotechnology research. EPA can use its limited resources, which
otherwise would be used to review these low risk research activities
for microorganisms, for reviewing higher risk activities and
microorganisms. Industry, by having this exemption, can develop and
test microorganisms in the early stages of the product development
process (e.g., laboratory) without having to be reviewed by EPA. This
would reduce the time and cost for industry in developing new products.
More time and resources could be allotted for actual R&D and less time
and resources allotted to EPA notifications. This should assist the
development of this industry and the emergence of new, useful products,
and thus not present an unreasonable risk of injury to human health and
the environment.
5. Alternative methods of reducing the number of microorganisms
emitted. EPA believes its proposed approach to reducing the number of
microorganisms emitted from research facilities is preferable to more
prescriptive approaches which have been suggested. The suggested
approaches include setting a specific numerical standard for the number
of microorganisms that might be incidentally released to the
environment from a research facility, prescribing a single standard
based on one of the containment levels described in the NIH Guidelines,
or an approach wherein several increasingly stringent levels of
containment are described and specific microorganisms are matched to
specific levels. These three approaches would be complex and unwieldy
to implement. Because of their prescriptive nature, such approaches
would result in EPA regulating the containment standards rather than
exempting the research. This would unnecessarily restrict research
contrary to the intent of TSCA. Each change to a prescriptive standard
would have to be incorporated into the standards through rule
amendments or variance procedures. Establishing prescriptive standards
could restrict advances in technology for controlling microorganisms
and stifle individual initiative at the research level.
C. Section 5(h)(4) Exemptions
1. Introduction--a. Statutory background. Section 5(h)(4) of TSCA
provides that EPA may exempt by rule the manufacture of any new
chemical substance from all or part of the requirements of section 5,
if it is determined that activities involving the substance will not
present an unreasonable risk of injury to health or the environment. A
section 5(h)(4) rule must be promulgated under the procedures set forth
in TSCA sections 6(c)(2) and (3), which generally require preparation
of a rulemaking record and an administrative hearing. EPA is proposing
to use section 5(h)(4) to support various exemptions from the
notification requirements of the rule.
The term ``unreasonable risk'' is not defined in TSCA. Section 6(c)
of TSCA lists considerations for determining whether a chemical
substance presents an unreasonable risk for purposes of promulgating
regulations under TSCA section 6. These considerations include the
effects of the substance on human health and on the environment and the
magnitude of exposure to the substance, the benefits of the substance
for various uses, the availability of substitutes for such uses, and
the reasonably ascertainable economic consequences of the potential
regulatory action, considering effects on the national economy, small
business, technological innovation, the environment, and public health.
EPA believes it is reasonable to consider these factors in determining
whether a risk is unreasonable under section 5(h)(4).
TSCA offers no further direct guidance on what constitutes
unreasonable risk. In particular, TSCA does not discuss how each of the
section 6(c) considerations are to be weighed in relation to each
other. The legislative history, therefore, needs to be considered. The
House Report (H.R. Rep. 94-1341, 94th Cong., 2d Sess. at 13-15, 32)
provides the most useful pertinent explanation. First, the standard
under TSCA is ``unreasonable'' risk, not a decision to eliminate all
risk (House Report at 15). For an activity that is of some value to
society, some level of risk may be acceptable. With respect to section
5(h)(4), granting an exemption does not require a showing that there
will be no risk, only that there will be no unreasonable risk.
The House Report states that the unreasonable risk standard cannot
be defined in precise terms but, instead, requires exercise of judgment
by the decisionmaker. The House Report describes the finding of
unreasonable risk as involving a balancing of the probability that harm
will occur, and the magnitude and severity (potential consequences) of
that harm, against the effects (social and economic) of proposed action
on society.
According to the House Report, these evaluations of harm often must
be based on considerations of ``scientific theories, projections of
trends from currently available data, modeling using reasonable
assumptions, and extrapolations from limited data'' (House Report at
32). The unreasonable risk standard recognizes that, as a practical
matter, all the scientific evidence is uncertain to some degree and
that EPA can consider such factors as the strength of the evidence on
toxicity, the nature of the effects that may occur (e.g., death vs.
reversible effects), and the likely numbers of individuals exposed and
the levels of exposure.
The House Report points out that the unreasonable risk standard is
flexible enough to allow EPA to calibrate the stringency of a
regulatory measure to the levels of risks and benefits. Thus, a testing
rule, because it does not deprive the public of the benefits of a
chemical, requires a lesser showing of harm compared to a rule which
may remove a substance from the market or impose other restrictions on
its availability. Similarly, a stronger showing would be required to
ban an activity than to impose lesser restrictions on use or a
requirement, such as labelling, that does not restrict directly.
The greater the probability and the more severe the potential harm
presented by an activity EPA may allow, the less likely a no
unreasonable risk finding can be made. Similarly, the greater the
benefit of the activity, the greater the risk to be tolerated.
Determinations of whether an exemption should be partial or full will
depend on the probability and severity of the harm and the benefits to
be derived from the activity. Less restrictions should apply if there
are substantial benefits from the activity and the probability of harm
appears to be lower or the consequences are of low concern.
b. Summary of section 5(h)(4) exemptions. EPA is proposing to use
its authority under TSCA section 5(h)(4) to establish six separate
types of exemptions. These are partial exemptions that involve limited
reporting and/or recordkeeping for new microorganisms that meet the
eligibility requirements of the specific exemptions. Five of these
exemptions specifically relate to R&D activities. The sixth case is a
tiered exemption for general commercial use.
Because each exemption involves a different set of issues, each
exemption requires a different weighing of risks and product benefits.
The remainder of this unit sets out the no unreasonable risk findings
for each of the exemptions. For each exemption, a review of the
relevant scientific risk considerations is followed by a discussion of
the social and economic benefits resulting from microbiological
products. The extent to which both risks and benefits are considered is
dependent on the breadth of the exemption.
2. Alternative finding of no unreasonable risk for microorganisms
used for R&D in contained structures. The reasoning for this
alternative finding relies on the factors discussed in Unit III.B. of
this preamble for research that meets the criteria at proposed
Secs. 725.234 and 725.235 for R&D conducted in contained structures.
See Unit III.B. of this preamble for a full discussion of the rationale
for exempting research in contained structures.
3. Deferral to other Federal authorities for oversight of R&D. Unit
II.D. of this preamble describes a proposed exemption from this
regulation for research controlled by other federal authorities. This
section provides EPA's reasons for establishing this exemption. The
exemption is based on the general policy that TSCA should not apply to
research adequately overseen by other federal authorities.
TSCA jurisdiction is discussed in Unit I.C. of this preamble.
Generally microorganisms controlled by other Federal agency
authorities, other than those microorganisms regulated under FIFRA or
FDA authorities, are also subject to TSCA. Agencies, such as the Animal
and Plant Health Inspection Service (APHIS) of the U.S. Department of
Agriculture (USDA), have regulatory authority that overlaps TSCA
authority for microorganisms. Research subject to TSCA may also be
funded by Federal agencies, such as the Department of Defense (DOD),
the Department of Energy (DOE), the National Institutes of Health
(NIH), the National Science Foundation (NSF), USDA's APHIS or its
Office of Science and Education (S&E), or EPA's own Office of Research
and Development (EPA/ORD).
On November 23, 1976, all Federal agencies represented on the
Federal Interagency Committee endorsed the NIH Guidelines. Departments
which support or conduct laboratory rDNA research agreed to abide by
the Guidelines in June 1983 (48 FR 24577). Because of the 1983
agreement, as a condition for Federal funding of rDNA laboratory
research, institutions must ensure that all rDNA research conducted at
or sponsored by the institution, regardless of the source of the
funding, complies with the Guidelines.
a. Finding of no unreasonable risk for R&D in contained structures
subject to the authority of other Federal agencies. This proposed rule
would provide an exemption for research in contained structures
(principally laboratories) covered by the NIH Guidelines. EPA considers
the NIH Guidelines to provide the primary standard for laboratory
research. EPA's rules are designed to provide complementary oversight
of those activities not covered by NIH. As a result, EPA is proposing a
complete exemption under TSCA section 5(h)(4) for research on new
microorganisms in contained structures, if the researcher is required
to comply with the NIH Guidelines. This may be achieved through direct
regulatory authority or through requiring recipients of Federal funds
to comply with the NIH Guidelines. Without this exemption, the
recordkeeping and employee notification requirements of proposed
Secs. 725.234 and 725.235 would apply to this research. EPA's summary
analysis of the NIH Guidelines may be found in the docket which
supports this rulemaking.
EPA proposes under TSCA section 5(h)(4) to exempt from the
requirements described in proposed Secs. 725.234 and 725.235 the
manufacturers, producers and importers of new microorganisms for R&D in
contained structures, if the research is regulated or funded by a
Federal agency which has agreed to abide by the NIH Guidelines.
The pertinent parts of EPA's regulations applying to R&D in
contained structures are Sec. 725.234(b) and (d). They require a
technically qualified individual (TQI) to maintain documentation that
describes the selection of containment and inactivation procedures and
ensures the procedures are followed. The TQI's selections must be
approved and certified by an authorized official of the institution
conducting the experiment (Sec. 725.234(d)(2)). EPA may request the
records, review containment/inactivation controls and may order changes
in containment/inactivation procedures (Sec. 725.234(d)(3) and (d)(4)).
These provisions are designed to complement the NIH Guidelines and
extend their benefits, without imposing an overly rigid regulatory
regime. EPA's regulation is in the same spirit as the NIH Guidelines in
that it is also based on the fact that all conceivable experiments
cannot be foreseen and that it is the responsibility of the
experimenting institution to devise appropriate containment. Like NIH,
EPA emphasizes the importance of the motivation and good judgment of
the investigators.
Because the NIH Guidelines are very well entrenched in the research
community, EPA expects that the procedures chosen by the TQI will very
closely follow the Guidelines. In addition, any EPA review of records
will rely heavily on the Guidelines. Thus, by establishing the
provisions of proposed Sec. 725.234(d), EPA would effectively apply
Guideline principles to those institutions, primarily commercial
facilities, that are not required to abide by them. This would
complement the NIH request for voluntary compliance.
Further, the NIH Guidelines apply directly only to those
microorganisms, and categories of microorganisms, that have been listed
in the Guidelines and, in particular, Guideline Appendices A through F.
Other microorganisms would require specific review by NIH. EPA
regulations extend the benefits of the NIH Guidelines by effectively
applying their principles to microorganisms other than those
specifically mentioned in the Guidelines.
At the same time, by not incorporating the Guidelines directly into
regulations, EPA would avoid overly rigid adherence to Guidelines that
are, themselves, meant to be flexible. EPA, however, retains sufficient
control to protect against risk by the review procedures in proposed
Sec. 725.234(d)(3) and (d)(4).
Requiring researchers to adhere to the proposed requirements of
Secs. 725.234 and 725.235 as well as to the requirements of these other
federal authorities would be a duplication of oversight and enforcement
that would unnecessarily restrict potentially beneficial research
without any incremental reduction in potential risk. Thus, there would
be no increase in risk from removing the TSCA section 5 restrictions
placed on contained structure R&D. Further, costs will be reduced,
because there would be no costs incurred in complying with TSCA. R&D
would be encouraged without an attendant increase in risk. Therefore,
the risks of exempting this research from the TSCA section 5 contained
structure R&D restrictions are far outweighed by the costs saved.
Accordingly, EPA finds there will be no unreasonable risk from this
exemption.
b. Federal agency R&D subject to TERA reporting. EPA has also
considered how it might use its TSCA section 5(h)(4) exemption
authority to minimize duplicative reviews of environmental release
tests that are also subject to other Federal agencies. EPA has
determined that a different exemption process should apply to
experiments in the environment than to contained experiments. While the
NIH Guidelines are recognized as a standard for contained R&D, the same
situation does not pertain to R&D activities involving releases to the
environment. Accordingly, EPA is planning to propose the procedures
outlined below for exemptions from the TERA process for deliberate
release experiments reviewed by other Federal agencies.
With agencies that have clear regulatory authority, EPA would
propose to exempt from TSCA section 5 requirements intentional
environmental testing of new microorganisms and to defer to the other
Federal agency's review, when EPA determines that the other Federal
agency's review addresses criteria equivalent to those which would be
evaluated under TSCA section 5. When EPA develops such an exemption
involving deferral to another Federal agency, it will propose the
exemption using notice and comment rulemaking. EPA is currently working
with USDA-APHIS to develop an exemption for R&D field tests reviewed by
APHIS under the Federal Plant Pest Act and the Plant Quarantine Act and
implementing regulations at 7 CFR part 340 and hopes to include such an
exemption when the rule is promulgated.
4. Finding of no unreasonable risk for TERA approval of new
microorganisms--a. Background. EPA recognizes that many small-scale
tests will not present unreasonable risks and that requirements
restricting R&D could stifle innovation contrary to the intent of TSCA.
Therefore, under section 5(h)(4) EPA is proposing to conditionally
exempt from MCAN notification R&D involving certain new microorganisms.
The exemption is conditional, since researchers must submit a TERA.
EPA's current experience with reviewing PMNs for microorganisms
used for R&D in the environment under the 1986 Policy Statement has
indicated that EPA could more efficiently review these activities.
While the current process provides an adequate mechanism, R&D
activities present a very different risk assessment situation than
general commercial use. Differences in exposure, the ability to apply
procedures for controlling routes of exposure or dissemination and the
procedures for controlling potential risks, and the need for
flexibility in R&D comprise different risk assessment scenarios than
found in general commercial use. As a result, in light of these
different scenarios, a more straightforward and flexible approach to
reviewing experiments for new microorganisms is indicated. The TERA
provisions of this proposed rule will provide such an approach.
A TERA provides for submission of information commensurate with the
nature of the R&D process, because the review is focused on a specific
R&D activity. Therefore, not as much information is required compared
to a MCAN. For example, persons who submit a TERA would not have to
include information on all commercial manufacture, processing,
transport, use, and disposal activities that may involve the new
microorganism as is the case for a MCAN.
The more flexible deadlines and procedures for the TERA would avoid
unnecessary delays or restrictions on experiments. TSCA imposes a 90-
day waiting period for section 5(a)(1) screening; and persons who
submit MCANs must wait at least 90 days before an activity can begin,
even if EPA should determine no unreasonable risk is posed by the
activity before the 90-day review period expires. A similar waiting
period may not be appropriate for experiments when more rapid decisions
can be made. If TERA review shows that an experiment poses little or no
risk, EPA could notify the submitter to proceed at any time during the
review period prior to expiration of the review clock.
b. No unreasonable risk determination. EPA has decided that case-
by-case review is required to determine the potential risk presented by
a microorganism which may establish in the environment during the
course of a field trial. The review would allow EPA to determine if it
would be necessary to set limitations to minimize the probability of
establishment and dissemination in the environment. Microorganisms
intentionally tested in the environment are more likely to be
acclimated to the environment into which they are introduced, be
physiologically fit enough to be competitive in that environment for a
significant period of time, and be placed in an area suitable for
growth and persistence. Researchers generally apply large numbers of
microorganisms to ensure that they persist long enough and compete well
enough to perform the function the researcher intends to study. This
fact increases the probability that microorganisms used under these
conditions could establish and possibly pose a risk or result in
significant exposure. Therefore EPA has concluded that R&D which
involves intentional testing of microorganisms in the environment
should be subject to some review.
EPA has balanced a number of considerations to determine that
experiments reviewed under a TERA will not present an unreasonable risk
to health or the environment and should be exempt from MCAN
requirements. First, TERA review should result in no greater risks than
those that might occur as a result of the MCAN process, because the no
unreasonable risk criteria for approval are the same for either
process. Second, TERA review may even reduce risks in some instances by
allowing EPA to focus resources on activities that may pose the
greatest potential for risk. Third, TERA review will reduce reporting
costs by eliminating Agency need for information and procedures that
are unnecessary for R&D. Fourth, when compared to the MCAN process,
TERAs should encourage technological innovation and have a beneficial
effect on small businesses engaged in R&D utilizing new microorganisms.
5. Finding of no unreasonable risk for microorganisms proposed for
exemption from TERA reporting. EPA recognizes that some field
experiments with new microorganisms do not need to be reviewed at all.
EPA therefore intends to exempt from review some R&D experiments with
certain new microorganisms. EPA will, however, still review any general
commercial uses of these new microorganisms through the MCAN process.
The no unreasonable risk finding for exemption from TERA reporting is
based on the interaction of three principal criteria addressing the
recipient species, the introduced genetic material, and procedures for
limiting exposure during experimental use. The three criteria must be
considered in concert, because any potential concerns raised in one set
of criteria may be balanced or compensated by other criteria. These
criteria are discussed in more detail in Unit III.C.7. of this
preamble.
EPA requests comment on whether this approach should be used to
exempt from TERA screening certain new microorganisms. EPA is proposing
certain intergeneric strains of Bradyrhizobium japonicum and Rhizobium
meliloti as candidates for exemption from TERA review, based on reviews
of voluntary PMNs submitted under the 1986 Policy Statement and field
test data generated in these field trials. Persons possessing
information which they believe would support an exemption from TERA
reporting for other new microorganisms may use the procedures in
proposed Sec. 725.67 to apply for such an exemption.
EPA proposes to list Bradyrhizobium japonicum and Rhizobium
meliloti as acceptable recipient species. Both are well-characterized
taxonomically and have been used in the environment for over 80 years
to improve nitrogen fixation in specific agricultural crops. There is
extensive information on these two species documenting the lack of
adverse effects in the environment, and no reports exist that they are
pathogenic to humans or animals. In addition, EPA has reviewed field
test data from several experiments which have demonstrated that the
intergeneric strains are similar to the unmodified parental strains in
colonization, survival, nodulation and effects on plant growth. The
public dockets pertaining to the reviews of B. japonicum (six strains:
P88-1275 through 1278, and P89-340 and 341) and R. meliloti (18
strains: P87-568 through 570, P88-1115 through 1122, P89-280, P90-339,
and P92-399 through 403), along with the field test data, are
incorporated into the docket for this rulemaking. These strains were
modified in antibiotic resistance traits, and some were modified for
nitrogen fixation traits as well. In the course of these reviews, EPA
evaluated general and specific information in the open scientific
literature concerning these species, and BSAC subcommittees were
convened to discuss general issues associated with the proposed R&D
experiments with these strains.
Modification of traits, the second criterion, limits the source of
the introduced genetic material to the genera of Rhizobium and
Bradyrhizobium but allows the introduction of antibiotic resistance
traits from any source organism. In addition, the introduced genetic
material must be poorly mobilizable. The introduction of genetic
material for traits other than antibiotic resistance is limited to
Bradyrhizobium and Rhizobium species, because EPA is most familiar with
these two genera.
Based on the results of the field tests with these strains, EPA
proposes to exempt the use of well-characterized, limited in size, and
poorly mobilizable antibiotic resistance markers in Bradyrhizobium
japonicum and Rhizobium meliloti. EPA believes that there would be no
significant risk resulting from small-scale field tests with the
resulting microorganisms containing antibiotic resistance, because
broad antibiotic resistance already exists in naturally occurring
microorganisms of these two species (as demonstrated in the data
submitted for PMNs P88-1115 (rhizobia) and P88-1275 (bradyrhizobia). In
addition, higher levels of antibiotic resistance can be easily induced
in these microorganisms by mutation or selection. EPA requests comment
on the appropriateness of exempting antibiotic resistance traits.
EPA is proposing that these exemptions would only apply to test
sites of 10 acres or less. This test area limit for Bradyrhizobium
japonicum and Rhizobium meliloti is based on the field data reviewed by
EPA which show that such releases have remained small-scale, with the
modified strains exhibiting survival and persistence similar to their
unmodified parental strains. The TQI must select appropriate methods to
limit dissemination of these modified rhizobial species in order to
maintain the small-scale nature of the field tests. Also, this proposal
is based on the lack of adverse effects observed in humans and animals
resulting from use of these naturally occurring rhizobial species.
EPA is proposing to exempt intergeneric strains of these two
rhizobia species, in order to facilitate research using these
microorganisms and to encourage development of products that could
increase crop productivity while decreasing dependance on chemical
fertilizers. These experiments could generate important information
that will increase understanding of the environmental fate of
intergeneric microorganisms. Information from these field tests would
advance the understanding of microbial ecology, which could facilitate
review of commercial products. The possible risks due to exempting
these two rhizobia species from review at small-scale will be balanced
by the innovation and development of safer, environmentally sound
products to promote crop production.
6. Finding of no unreasonable risk for specific alternative
exemption for low risk field tests. Unit II.D. of this preamble
describes an alternative exemption from TERA reporting for certain R&D
field tests. While EPA acknowledges that parts of the rationale offered
in Unit III.B. of this preamble for exempting research conducted under
the proposed contained structures exemption could be applied to some
small-scale field tests involving microorganisms, EPA does not believe
that the rationale can be applied to small-scale field tests as a
class. Therefore, it was suggested that EPA define a class of small-
scale field tests which would be expected to pose low risks and be
exempt from TERA reporting. The no unreasonable risk finding for this
alternative exemption from TERA reporting is based on the interaction
of three primary criteria which consider the safety of the parent
microorganism, the role of the traits that have been modified, and the
scale of the field tests. If the parent microorganism is shown to have
a history of safe use, introduced genetic material meeting the
specified criteria would be unlikely to significantly increase the
potential for adverse effects. EPA would expect that TQIs would use the
criteria discussed in III.C.7. of this preamble for the recipient
microorganism and the introduced genetic material as guidance in
determining that their new microorganisms would be eligible for this
exemption. As in the contained structures exemption for R&D, EPA is
relying on the experience and judgement of the TQI to select
appropriate methods to limit dissemination of the new microorganisms in
order to maintain the small-scale nature of the field tests. Reliance
on the judgement of the TQI is discussed further in Unit III.B. of this
preamble. EPA believes that the criteria it has specified circumscribe
a category of field tests which can be considered low risk. In
addition, should EPA receive a notice for a planned field test which
did not appear to be low risk, EPA could require the submission of a
TERA in order to review more completely the proposal.
EPA believes that the field tests potentially eligible for this
alternative exemption could generate important information which will
generally advance the understanding of microbial ecology and
specifically facilitate EPA's review of intergeneric microorganisms.
The low risks posed by the field tests will be balanced by benefits in
the form of reduction in reporting burden for researchers and the
encouragement of innovation in the development of environmentally sound
products. EPA would like to receive public comment on whether the
benefits of this exemption outweigh the potential risks posed by small-
scale field tests eligible for the exemption.
Although field tests which meet the proposed criteria would be
considered to pose low risks, additional concerns could be raised for
unlimited uses of the same microorganisms at the general commercial use
stage. Once development of these microorganisms moves beyond R&D to
general commercial use, they would be subject to the MCAN reporting
requirements discussed in Unit II.C. of this preamble.
7. Finding of no unreasonable risk for new microorganisms eligible
for tiered commercial use exemption. EPA recognizes that some
microorganisms present a low risk when used under specific conditions
at general commercial use. Therefore, EPA is proposing expedited
processes for certain microorganisms at the general commercial use
stage. The requirements and processes for the Tier I and Tier II
exemptions are discussed in Unit II.C. of this preamble. The criteria
for Tier I and Tier II exemptions address: (1) The recipient
microorganism; (2) the introduced genetic material; and (3) performance
based standards for minimizing the numbers of microorganisms emitted
from the manufacturing facility.
To evaluate the potential for unreasonable risk to human health or
the environment in developing these exemptions, EPA focused primarily
on the characteristics of the recipient microorganisms. If the
recipient is shown to have little or no potential for adverse effects,
introduced genetic material meeting the specified criteria would not
likely significantly increase potential for adverse effects. As further
assurance that risks would be low, EPA is also specifying procedures
for minimizing numbers of organisms emitted from the facility. When
balanced against resource savings for society and expected product
benefits, these exemptions will not present unreasonable risks.
a. The recipient microorganism. Six criteria were used to determine
eligibility of recipient microorganisms for the tiered exemption.
First, it should be possible to clearly identify and classify the
microorganism. Available genotypic and phenotypic information should
allow the microorganism to be assigned without confusion to an existing
taxon which is easily recognized. Second, information should be
available to evaluate the relationship of the microorganism to any
other closely related microorganisms which have a potential for adverse
effects on human health or the environment. Third, there should be a
history of safe commercial use for the microorganism. Fourth, the
commercial uses should indicate that the microorganism products might
be subject to TSCA jurisdiction. Fifth, studies are available which
indicate the potential for the microorganism to cause adverse effects
on human health and the environment. Sixth, studies are available which
indicate the survival characteristics of the microorganism in the
environment. EPA requests comment on whether these are the appropriate
criteria to consider to determine the eligibility of recipient
microorganisms for the tiered exemption. After each microorganism was
reviewed using the six evaluation criteria, a decision was made to
place the microorganism on the list in proposed Sec. 725.420. Summaries
of the individual risk assessments, are discussed below. The full risk
assessments for the recipient microorganisms are in the docket for this
proposed rulemaking.
(i) Acetobacter aceti is an obligate aerobic bacterium naturally
found in the restrictive niche of fermenting fruit, where it can
tolerate and utilize ethanol as a nutrient. This species has no
recorded pathogenicity on plants, humans, or animals and has a history
of safe industrial use. A. aceti is well-defined taxonomically and
clearly distinguished from other Acetobacter species known to cause the
browning of processed fruit. While it can be expected to survive in the
environment, A. aceti is unlikely to cause any significant
environmental effects.
(ii) Aspergillus niger is an asexual fungus commonly found
degrading organic matter in nature. This organism has a history of safe
use for the production of citric acid and several enzymes. It has been
shown to be an opportunistic human pathogen and to damage several
species of plants. While production of certain mycotoxins has been
associated with strains of A. niger, companies have been using
naturally occurring strains of A. niger to produce a variety of
products for many years without reports of toxic effects of workers.
The limited in size constraints as well as the restriction on
vertebrate toxins imposed on introduced genetic material by the
criteria for the tiered exemption should reduce the likelihood of
increased production or exposure to malformins A and C, the two most
potent mycotoxins potentially produced by A. niger strains. In general,
the restrictions placed on the introduced DNA and containment mean that
the recombinant A. niger strains eligible for the tiered exemption
should pose no greater risks than naturally occurring strains of A.
niger.
(iii) Aspergillus oryzae is an asexual fungus found in nature and
used for hundreds of years in the production of soy sauce, miso and
sake without recorded incidents. This fungus has no reported adverse
effects on either plants or animals. It has been suggested that genetic
engineering of A. oryzae might inadvertently produce an aflatoxigenic
strain. Naturally occurring strains of A. oryzae are not known to
produce aflatoxins; however, some scientists believe that A. oryzae is
a domesticated version of A. flavus and may possess dormant genes for
aflatoxin production. It is likely that companies have already been
using genetically modified strains of A. oryzae, but these strains have
not yet met the PMN reporting requirements, that is, they are not
intergeneric. The limitations placed by the tiered exemption on the
introduced genetic material, in particular the well-characterized and
limited in size restrictions, should reduce the likelihood that any
sequences relating to aflatoxin production could be introduced. The
containment requirements would limit exposure to any mycotoxins
produced. In addition, A. oryzae does not colonize humans. In general,
the restrictions placed on the introduced genetic material and
containment mean that the recombinant A. oryzae strains eligible for
the tiered exemption should pose no greater risks than naturally
occurring strains of A. oryzae.
(iv) Bacillus licheniformis is an aerobic sporeforming bacterium
that is well defined taxonomically. It can be readily isolated from the
environment, where it persists primarily as endospores. Many strains
have been tested and shown to have no adverse effects on humans,
animals or plants. B. licheniformis has been reported as an
opportunistic pathogen in livestock; however, it has never been
diagnosed as a causal agent. B. licheniformis has a history of safe use
in large-scale fermentation production of specialty chemicals and
substances such as citric acid and detergent enzymes. Although the
majority of experience with industrial fermentations employing B.
licheniformis is with asporogenic strains, all strains of this
microorganism are being recommended for the tiered exemption.
(v) Bacillus subtilis is an aerobic sporeforming bacterium which is
not completely defined at either the genus or species level. This
species is commonly found in nature, particularly in terrestrial
environments. Many strains have been tested and shown to have no
adverse effects on humans, animals or plants. Reports of B. subtilis
acting as an opportunistic pathogen are few in number and have not been
well substantiated. B. subtilis has a history of safe use in large-
scale fermentation production of specialty chemicals and enzymes and
even as a source of single cell protein for human consumption in Asia.
Although the majority of experience with industrial fermentations
employing B. subtilis is with asporogenic strains, all strains of this
microorganism are being recommended for the tiered exemption.
(vi) Clostridium acetobutylicum is an obligate anaerobic endospore-
forming bacterium which has been isolated from soils, sediments, well
water, and from animal and human feces. Various strains of C.
acetobutylicum have a history of safe use industrially or in research
for the production of butanol and acetone from various feedstocks.
While C. acetobutylicum may survive in the environment, it is not
likely to cause any significant environmental effects. Although the
current taxonomic classification of Clostridium species is not well-
defined, C. acetobutylicum can be distinguished from closely related
species which are known to be human pathogens. In general, the
restrictions placed on the introduced genetic material and containment
mean that the recombinant C. acetobutylicum strains eligible for the
tiered exemption should pose not greater risks that the naturally
occurring strains of C. acetobutylicum which have been used in industry
without reports of adverse effects to workers or the environment.
(vii) Escherichia coli K-12 is a strain which is well defined
taxonomically, although the genus Escherichia as a whole is not. E.
coli K-12 strains can be readily distinguished from those close
relatives that are pathogens. E. coli K-12 is a debilitated bacterium
which does not normally colonize the human intestine. It has also been
shown to survive poorly in the environment, has a history of safe
commercial use, and is not known to have adverse effects on humans,
microorganisms, or plants. Although some K-12 substrains produce low
levels of toxins, toxin expression by these substrains is mitigated by
E. coli K-12's poor survival in the environment and its inability to
colonize normal human or animal hosts.
(viii) Penicillium roqueforti is an asexual fungus which decomposes
organic materials in nature. Most strains of P. roqueforti, including
those used in cheese production, have been shown capable of producing a
variety of mycotoxins. P. roqueforti's long history of use in the
production of blue cheese has shown no adverse effects. P. roqueforti
is generally considered to be a benign organism, but it does raise
concerns because of its ability to produce mycotoxins under certain
conditions. Despite these concerns, the organism has a history of use
without noted reports of adverse effects to workers or the environment.
In general, the restrictions placed on the introduced genetic material
and containment mean that the recombinant P. roqueforti strains
eligible for the tiered exemption should pose no greater risk than
naturally occurring strains of P. roqueforti.
(ix) Saccharomyces cerevisiae is a yeast that occurs commonly in
the environment. Although it is not well defined taxonomically and
survives well in the environment, it has a history of safe use in the
commercial production of many products (e.g., beer). Further, it is not
known to cause pathological effects on humans, plants, or animals. S.
cerevisiae has no known effects on microorganisms, other than possible
effects on strains of its own species.
(x) Saccharomyces uvarum is a yeast capable of fermenting a variety
of sugars into ethanol. S. uvarum has a long history of safe use in
production of alcoholic beverages and industrial ethanol. Although it
is expected to survive in the environment, it is not expected to cause
any adverse environmental effects. While S. uvarum has been used
industrially for years, specific strains have not been distinguished.
b. The introduced genetic material. In order to qualify for either
Tier I or Tier II exemption, any introduced genetic material must be
limited in size, well-characterized, free of certain nucleotide
sequences, and poorly mobilizable.
(i) Limited in size. Introduced genetic material must be limited in
size to those segments required to perform the intended function, as
described at proposed Sec. 725.421(a). This criterion reduces
uncertainty by excluding the introduction into a recipient of
extraneous and potentially uncharacterized genetic material. The
requirement that the regulatory sequences permit the expression solely
of the structural gene(s) of interest reduces risk by preventing
expression of genes downstream of the inserted genetic material. The
limitation on the vector sequences that are components of the
introduced genetic material prevents the introduction of novel traits
beyond those associated with the gene(s) of interest. The overall
result of the limited in size criterion is improved ability to predict
the behavior of the resulting microorganism. EPA requests comment on
the usefulness of this criterion in reducing uncertainty about the
behavior of the new microorganism and any difficulties researchers may
have in isolating the genetic material required to perform the intended
functions.
(ii) Well-characterized. The requirement at proposed
Sec. 725.421(b) that the introduced genetic material be well-
characterized also contributes to improved ability to predict the
behavior of the resulting microorganism. Well characterized includes
knowledge of the function of the introduced sequences and the
phenotypic expression associated with the introduced genetic material.
Genetic material which has been examined at the restriction map or
sequence level, but for which a function or phenotypic trait has not
yet been ascribed, is not considered well-characterized.
Well-characterized would include knowing whether multiple reading
frames exist within the operon. This relates to whether more than one
biological product might be encoded by a single sequence, and addresses
the possibility that a modified microorganism could display unpredicted
behavior should such multiple reading frames exist and their action not
be anticipated.
(iii) Free of certain sequences. In addition to improving the
ability to predict the behavior of the modified microorganism, the
well-characterized requirement ensures that segments encoding for
either part or the whole of the toxins listed at proposed
Sec. 725.421(d) would not inadvertently be introduced into the
recipient microorganism (Refs. 11 and 12).
The toxins listed at proposed Sec. 725.421(d) are polypeptides of
relatively high potency. Other types of toxins (e.g., modified amino
acids, heterocyclic compounds, complex polysaccharides, glycoproteins,
and peptides) are not listed for two reasons. First, their toxicity
falls within the range of moderate to low. Second, these types of
toxins generally arise from the activity of a number of genes in
several metabolic pathways (multigenic).
In order for a microorganism to produce toxins of multigenic
origin, a large number of different sequences would have to be
introduced and appropriately expressed. It is unlikely that all of the
genetic material necessary for metabolizing multigenic toxins would be
inadvertently introduced into a recipient microorganism when
requirements that the genetic material be limited in size and well-
characterized are followed. Should any of the necessary sequences not
be introduced, or not be expressed appropriately by the recipient, a
toxin of multigenic origin would not be produced. EPA, thus, sees no
reason why a manufacturer who wishes to modify a microorganism listed
in proposed Sec. 725.420 with a single or a few sequences involved in
metabolism of a multigenic toxin should not be allowed to do so.
Introduction of a single or a few such sequences into a candidate
microorganism should not result in production of a multigenic toxin and
thus would not present significant risk.
Similarly, other properties that might present risk concerns result
from the interactive expression of a large number of genes. For
example, pathogenic behavior is the result of a large number of genes
being appropriately expressed. Because of the complex nature of
behaviors such as pathogenicity, the probability is low that an insert
consisting of well-characterized, limited in size genetic material
could transform the microorganisms listed at proposed Sec. 725.420 into
microorganisms which display pathogenic behavior. For this reason, with
the exception of certain toxins which are listed because of their
potency, EPA is not listing at proposed Sec. 725.421(d) sequences that
are one of a series of sequences needed in combination in order for a
microorganism to display a complex behavior such as pathogenicity. If
commenters believe they can identify sequences which present risk
concerns which should be addressed and listed at proposed
Sec. 725.421(d), EPA requests they inform the Agency of these
sequences.
(iv) Poorly mobilizable. The requirement, at proposed
Sec. 725.421(c), that the introduced genetic material be poorly
mobilizable reduces potential for transfer of introduced genetic
sequences to other microorganisms in the environment. Such transfers
would occur through the interaction of the introduced microorganism
with indigenous microorganisms through conjugation, transduction, or
transformation. Through such transfers, the introduced genetic material
could be transferred to and propagated within different populations of
microorganisms, including microorganisms which may never previously
have been exposed to this genetic material. It is not possible to
predict how the behavior of these potential recipient microorganisms
will be affected after uptake and expression of the genetic material.
Since EPA is not limiting the type of organism that can serve as
the source for the introduced genetic material, some limitation is
placed on the ability of the introduced genetic material to be
transferred. This limitation mitigates risk by significantly reducing
the probability that the introduced genetic material would be
transferred to and expressed by other microorganisms.
The transfer frequency of 10-8 was selected as defining
``poorly mobilizable'' for four reasons. First, it represents the lower
end of the range of transfer frequencies observed in nature. Transfer
of plasmids, for example, commonly occurs through conjugation between
bacteria at rates ranging from no detectable transfer (typically less
than 10-8 transfer events per donor) to 10-2 transfer events
per donor in soil, water and sewage (Ref. 13). A similar range of
transfer frequencies has been associated with transduction of
chromosomal and plasmid DNA in soil and aquatic microcosms (Refs. 14,
15, and 16). Also, a limited number of studies on natural
transformation have documented a range of transformation events from
0.3 x 10-8 to 1 x 10-8 transformants per recipient (Ref. 17).
Second, studies of certain genetic traits (e.g., amino acid auxotrophy,
resistance to antibiotics) suggest the spontaneous rate of mutation to
be within the range of 10-5 to 10-8 per cell generation
(Refs. 18 and 19). A frequency of 10-8 appears to represent,
therefore, a baseline frequency at which change occurs in genetic
material. Third, this frequency sets the technical limit for
measurability. Below the rate of spontaneous mutation, it becomes
difficult to distinguish gene transfer from mutation. Fourth, the
10-8 criterion should not be difficult to meet, and, in fact, is a
standard employed in the NIH Guidelines.
The 10-8 frequency is attainable given current techniques.
Plasmids with transfer rates of 10-8 exist or are easily
constructed. In bacteria this low rate is readily engineered through
the inactivation of the transfer functions of mobile genetic elements,
or the inactivation/removal of pilus formation functions of plasmids
(Ref. 20). Some of the plasmids most commonly employed as vectors in
genetic engineering (e.g., pBR325 and pBR322) have mobilization/
transfer frequencies of 10-8 or less. The plasmid pBR322 has been
used as a vector to construct several microorganisms reviewed by EPA
under the 1986 Policy Statement.
The criteria set for ``poorly mobilizable'' for transduction and
transformation should not prevent most microorganisms from meeting the
exemption criteria, since the majority of transfer frequencies reported
for transduction and natural transformation are less than 10-8.
Higher frequencies are likely only if the introduced genetic material
has been altered or selected to enhance frequency.
Fungal gene transfer has also been considered in development of the
poorly mobilizable criterion. Although mobile genetic elements such as
transposons, plasmids, and double stranded RNA exist in fungi and can
be readily transferred, this transfer usually is only possible between
members of the same species during anastomosis, a process specific to
fungi. Since anastomosis only occurs between members of the same
species, the introduced genetic material would not be transferred to
distantly related fungi as may occur with bacteria.
Based on suggestions made at the July 22, 1991 BSAC Subcommittee
meeting, EPA proposes the following definition for ``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.'' For
microorganisms with introduced genetic material associated with
conjugative plasmids or conjugative transposons, this criterion can be
met by inactivation of transfer or mobilization functions which reduce
transfer frequency. In instances where introduced genetic material is
located on the chromosome, steps can be taken to insure a low transfer
frequency by transduction and transformation by reducing opportunities
for illegitimate recombination. EPA requests comment on the
appropriateness of its definition of poorly mobilizable and whether
there are alternative or additional methods for demonstrating that
introduced genetic material is poorly mobilizable that should be
included in the definition.
(v) Effect of introduced genetic material criteria. The
requirements placed on the introduced genetic material, in concert with
the level of safety associated with the recipient microorganisms,
ensure that the resulting microorganisms present low or negligible
risk. The probability is low that the insertion of genetic material
meeting EPA's criteria into such microorganisms will change their
behavior so that they would acquire the potential for causing adverse
effects. Risks would be mitigated by the four criteria placed on the
introduced genetic material, the relative safety of the microorganisms
listed at proposed Sec. 725.420, and the inactivation criteria
specified for the Tier I exemption. In the case of Tier II exemption,
risks would be mitigated in light of the four criteria placed on
introduced genetic material, the relative safety of the microorganisms
listed at proposed Sec. 725.420, and EPA's review of the conditions
selected.
c. Standards for minimizing the number of microorganisms emitted
from the facility. The standards prescribed for Tier I exemption
require that the structure(s) be designed and operated to contain the
microorganism, that access to the structure be limited to essential
personnel, that inactivation procedures shown to be effective in
reducing the number of viable microorganisms in liquid and solid wastes
be followed prior to disposal of the wastes, that features to reduce
microbial concentrations in aerosols and exhaust gases released from
the structure be in place, and that general worker hygiene and
protection practices be followed.
(i) Definition of structure. EPA considers the term ``structure''
to refer to the building or vessel which effectively surrounds and
encloses the microorganism. Vessels may have a variety of forms, e.g.,
cubic, ovoid, cylindrical, or spherical, and may be the fermentation
vessel proper or part of the downstream product separation and
purification line. All would perform the function of enclosing the
microorganism. In general, the material used in the construction of
such structure(s) would be impermeable, resistant to corrosion and easy
to clean/sterilize. Seams, joints, fittings, associated process piping,
fasteners, and other similar elements would be sealed.
(ii) Standards to minimize microbial release. EPA is proposing, for
several reasons, a somewhat cautious approach in prescribing standards
for minimizing the number of microorganisms emitted through the
disposal of waste and the venting of gases. First, a wide range of
behaviors can be displayed by microorganisms modified consistent with
EPA's standards for the introduced genetic material. Second, EPA will
not conduct any review whatsoever for Tier I exemptions. EPA believes
the requirement to minimize emissions will provide a measure of risk
reduction necessary for making a finding of no unreasonable risk. Taken
together, EPA's standards ensure that the number of microorganisms
emitted from the structure is minimized.
EPA's proposed standards for minimizing emission specify that
liquid and solid waste containing the microorganisms be treated to give
a validated decrease in viable microbial populations so that at least
99.9999 percent of the organisms resulting from the fermentation will
be killed. During normal fermentation processes, bacteria generally
reach a level of 1010 to 1011 colony forming units per
milliliter (Ref. 21). A simple calculation assuming no dilution of the
fermentor broth and a minimum inactivation efficiency of 99.9999
percent (or a 6 log reduction) results in an estimate of the
concentration of viable organisms released from the facility of at most
approximately 105 bacteria per milliliter. This number is likely
to be lower, since the required reduction is the minimum validated
inactivation and the actual kill is likely to be greater.
Fungi have greater biomass per colony forming unit and therefore
are incapable of reaching the high numbers that bacteria in
fermentation vats achieve. During the fermentation process, fungal
populations frequently reach population densities of 106 to
107 microorganisms per milliliter (Ref. 21). The proposed level of
inactivation would result in almost all fungi from the fermentation
process being rendered nonviable. Here too, the actual reduction in
number is likely to be greater that the minimum required by EPA.
Since the bacteria used in fermentation processes are usually
debilitated, either intentionally or through acclimation to industrial
fermentation, the small fraction of microorganisms remaining viable
after inactivation treatments will likely have a reduced ability to
survive during disposal or in the environment. This is because
microorganisms repeatedly cultured in specific growth conditions become
adapted to those conditions and often lose the ability to survive in
different conditions. This is particularly true when microorganisms are
used in industrial fermentations wherein most, if not all, of the
microorganism's nutritional and other needs are met to ensure rapid
growth and good product yield. Moreover, industrial companies, in an
attempt to keep their proprietary microorganisms from competitors and
to reduce the microbial numbers to those permitted by local sanitation
authorities, modify the microorganisms to increase the ability of their
microorganisms to survive and perform their assigned tasks in the
fermentor but decrease their ability to survive in the environment
external to the fermentor.
When treated wastes are placed in the sanitary sewage line during
disposal, factors such as changes in pH, temperature, ionic balance,
and dilution adversely affect any microorganisms remaining viable
subsequent to inactivation treatment. Similarly, when such wastes are
left in the form of cakes for several hours at room temperature, the
lack of nutrients and sufficient suitable electron acceptors (oxygen
for aerobes, other substances such as an organic compound or sulfur for
anaerobes) further reduces viability. Based on these considerations,
EPA believes that under its proposed standards, few viable
microorganisms will be emitted from the facility through the route of
liquid and solid wastes.
EPA requirements also address microorganisms in the exhaust from
the fermentor and along the production line. To address exhaust from
fermentors, EPA is proposing that the number of microorganisms in
fermentor gases be reduced by at least two logs prior to the gases
being exhausted from the fermentor. EPA selected 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.
Several studies cited by Battelle (Ref. 22) suggest that a typical
viable microorganism load in uncontrolled fermentor exhaust is about 5
x 104 organisms per cubic foot. A reduction of two logs would
reduce the number to approximately 5 x 102 microorganisms per
cubic foot. The actual number is likely to be lower, since the required
reduction is a minimum and the number removed may be greater.
The number of microorganisms that remain viable subsequent to being
exhausted from the fermentor is likely to be lower still. First, it is
generally not common industry practice to run fermentors in an
uncontrolled fashion. Second, microorganisms in fermentor exhausts
would be within aerosols. Aerosolization is, in general, very stressful
for microorganisms, because of the physical pressures associated with
aerosol formation and the high probability of dehydration (Refs. 22 and
23). Moreover, microorganisms that are physiologically acclimated to
the growth conditions within the fermentor are likely to be compromised
in their ability to survive aerosolization. EPA anticipates, therefore,
that few microorganisms will survive the stresses of aerosolization
associated with being exhausted in a gas from the fermentor. The
provision requiring reduction of microorganisms in fermentor exhaust
gases contributes to minimizing the number of viable microorganisms
emitted from the facility.
EPA requests comment on whether its standards for minimizing
releases of microorganisms from facilities are appropriate for this
exemption. EPA is particularly interested in whether commenters can
suggest reasonable alternative methods for reducing releases from
facilities and provide the rationale for these alternatives.
EPA is also proposing that the requirements specify that other
systems be in place to control dissemination of microorganisms by other
routes. This would include programs to control pests such as insects or
rats, since these might serve as vectors for carrying microorganisms
out of the fermentation facilities.
(iii) Worker protection. The requirement to minimize microbial
emissions, in conjunction with the requirement for general worker
safety and hygiene procedures, also affords a measure of protection for
workers. Potential effects on workers that exist with microorganisms in
general (e.g., allergenicity) will be present with the microorganisms
qualifying for this exemption. As with other substances that humans may
react to (e.g., pollen, chemicals, dust), the type and degree of
allergenic responses is determined by the biology of the exposed
individual. It is unlikely that a microorganism modified in keeping
with EPA's specifications for the introduced genetic material would
induce a heightened response. The general worker hygiene procedures
specified by EPA should protect most individuals from the allergenic
responses associated with microorganisms exhausted from fermentors and/
or other substances emitted along the production line. The EPA
requirement that entry be limited to essential personnel also addresses
this consideration by reducing to a minimum the number of individuals
exposed.
(iv) Guidance for Tier II. EPA is not specifying standards for
minimizing the number of microorganisms emitted from the facility for
microorganisms qualifying for Tier II exemption. Rather, the Agency
requests that submitters utilize as guidance the standards set forth
for Tier I procedures. The procedures proposed by the submitter in a
Tier II exemption request will be quickly reviewed by the Agency (45
days). EPA will have the opportunity to evaluate whether the procedures
the submitter intends to implement for reducing the number of organisms
emitted from the facility are appropriate for that microorganism.
d. Benefits of the tiered exemption. Substantial benefits are
associated with this proposed exemption. The recipient microorganisms
are already widely employed in general commercial uses subject to TSCA
reporting. These include microorganisms used to produce enzymes for
detergent use or biomass conversion, and production of specific
compounds such as plant or microbial growth promoting factors.
The Agency believes this exemption will result in resource savings
both to EPA and industry without compromising the level of risk
management afforded by the 90-day MCAN review. The microorganisms named
as recipients for the tiered exemption have been assessed for risk,
criteria limiting the potential for transfer of and expression of toxin
sequences have been provided, and the conditions of use are specified
in the exemption (Tier I) or will be reviewed by EPA (Tier II). EPA
requirements for minimizing numbers of viable microorganisms emitted
are within standard operating procedures for the industry, and both the
procedures and the structures specified in the exemption are the type
industry uses to protect their products from contamination.
The exemption will result in reduced reporting costs and a decrease
in delay associated with reporting requirements. The savings in Agency
resources can be directed to reviewing activities and microorganisms
which present greater uncertainty.
This exemption should facilitate development and manufacturing of
new products and the accumulation of useful information. When balanced
by the potential resource savings and many industrial benefits of these
microorganisms, the Agency finds the potential benefits of exempting
uses of these microorganisms under the specific criteria will not
present unreasonable risk.
EPA is considering designating other microorganisms as eligible for
this exemption, dependent upon risk assessments for these
microorganisms indicating that they present no unreasonable risk under
the conditions of use. A list of microorganisms EPA believes are used
by industry for TSCA uses appears in a support document in the docket
for this rulemaking. EPA plans to evaluate many of these to determine
whether they qualify as recipient microorganisms eligible for this
exemption. The goal of the evaluation is to ensure that the
microorganisms would present no unreasonable risk when used under the
conditions of this exemption. Persons possessing information
demonstrating no unreasonable risk and thus supporting eligibility for
the tiered exemption for these microorganisms or other microorganisms
are encouraged to submit such information to EPA to facilitate this
process. As noted previously, this information could be submitted using
the procedures at proposed Sec. 725.67.
IV. Other Issues
A. Microorganisms Covered in This Rulemaking
1. Microorganisms included. In this proposed rule, EPA, on the
advice of its BSAC, is including in its definition of ``microorganism''
those organisms classified in the kingdoms Monera (or Procaryotae),
Protista, and Fungi, the Chlorophyta and the Rhodophyta of the Plantae,
and viruses and virus-like particles. This definition, which uses the
five kingdom classification system of Whittacker (Ref. 24), includes,
but is not limited to bacteria, protozoa, fungi, mycoplasmas,
mycoplasma-like organisms, spiroplasmas, microphytoplanktons, and green
and red algae. Viruses and virus-like particles (e.g viroids,
satellites, virusoids) are also considered to be microorganisms by EPA,
even though they are classified in a unique classification system
described by Francki, et al. (Ref. 25). Should new categories of
organisms within the Monera, Protista, Fungi, and the Chlorophyta and
the Rhodophyta of the Plantae be identified, these also would be
considered microorganisms under this proposed rule. EPA requests
comment on its approach to the definition of microorganisms. EPA is
particularly interested in comment regarding the appropriateness of
including organisms from the Chlorophyta and the Rhodophyta of the
Plantae in its microorganism definition.
The organisms belonging to the Monera, Protista and Fungi are
primarily unicellular. Members of the Chlorophyta and the Rhodophyta
are also primarily unicellular. As members of the Thallophyta, they
show little if any tissue differentiation (the entire plant is known as
a thallus), the reproductive structures are often unicellular and lack
a protective wall or jacket of sterile cells, and the zygotes do not
form embryos within a female reproductive organ. The organisms of the
Monera, Protista, Fungi, Chlorophyta, and Rhodophyta may be prokaryotes
or eukaryotes, and may or may not possess cell walls.
Each type of microorganism can be significantly different, one from
another. Some measure of the differences between them can be seen in
the fact that the descriptor, ``microorganism'', spans four of the five
kingdoms into which all organisms are classified. These differences
present several challenges in constructing a rule.
2. Inclusion of viruses and virus-like particles. One important
consideration under TSCA revolves around the approach to viruses and
virus-like particles. Viruses are included by EPA in the designation
``microorganisms.'' These entities, which are among the smallest of
microorganisms, differ from other microorganisms in several ways.
First, they are non-cellular entities, lacking a delineating cell
membrane and the metabolic machinery for the basic cellular function of
energy generation. Second, they contain only one type of genetic
informational molecule, either RNA (ribonucleic acid) or DNA
(deoxyribonucleic acid). Third, viruses are obligate intracellular
inhabitants. They cannot reproduce independently outside of a host
cell. For this reason, viruses have historically been identified
according to the host they infect, i.e., plant viruses reproduce in
plant cells, animal viruses in animal cells, and bacterial viruses in
bacterial cells. There are also viruses of fungi, algae, and protozoa.
More recently a unique classification system has been developed based
on the genome structure and expression, as well as on structural
features of the virus particles (Ref. 25). Because their reproduction
within cells can result in disruption of the host cell, viruses are
generally considered to be pathogens. Viroids are virus-like particles
which are also pathogens. These entities are implicated in plant
diseases such as potato spindle tuber disease.
When the BSAC Subcommittee met on July 22, 1991, they considered
EPA's approach to microorganisms under TSCA. They raised several issues
with regard to viruses and virus-like particles. They noted that
viruses are by definition pathogens. As viruses in general have smaller
genomes than other microorganisms and a greater percentage of the
genome is related to pathogenicity, a change in the viral genome is
more likely to affect pathogenicity than a change in the genome of
microorganisms such as bacteria and fungi. Even when a change occurs
solely within a single genome, viruses and virus-like particles may
warrant a more cautious approach than other microorganisms. Finally,
plant and animal viruses are known to shift host range under in vitro
tissue culture conditions, other unique conditions, or in non-
traditional hosts, and this, in and of itself, is an important risk
consideration.
Thus, viruses and virus-like particles, because of their unique
characteristics, present different issues than other microorganisms.
This is particularly true of the viruses that attack macroorganisms
(humans, animals, and plants); and the use of these viruses probably
warrants scrutiny regardless of whether the virus is new or existing.
Viruses that infect other microorganisms (e.g., the viruses of
protozoa, fungi, and bacteria), may present a somewhat different risk
picture from those that infect macroorganisms. Although it appears
theoretically possible for a virus of a microorganism (also termed a
phage) to permanently eliminate its host microorganism from a habitat,
studies done to date do not provide strong evidence that this occurs
(Ref. 24), possibly because microorganisms are capable of rapidly
developing resistance to phage infection. Phage infections appear
rather to result in a temporary fluctuation rather than a permanent
change in the numbers of a microorganism in a specific habitat.
Moreover, redundancy in function found in natural microbial communities
(i.e., many species are capable of performing the same ecological
function (Ref. 5)) may cushion the effects of these population fluxes.
To address viruses for this rulemaking, EPA has distinguished
between those that infect microorganisms and those that infect
macroorganisms. Phages will be considered MGEs and the MGE guidance
discussed in Unit I.C. of this preamble will apply to them. Therefore,
a phage which has been modified to contain genetic material from a
second phage whose host microorganism is in a different genus than the
modified phage would be considered a ``new'' microorganism subject to
TSCA section 5 reporting. Similarly, a phage modified to contain
genetic material from an organism classified in a different genus than
the genus from which the modified (recipient) phage was isolated would
be considered intergeneric. Under this interpretation, a phage which
has been modified to contain genetic material from a virus of a
macroorganism would also be considered a ``new'' microorganism.
With regard to viruses of macroorganisms, EPA believes that certain
viruses of macroorganisms would be subject to TSCA jurisdiction if they
were employed in TSCA uses. As discussed in Unit I.C. of this preamble,
certain product uses are excluded from coverage under TSCA, the most
notable for viruses being the exclusions for pesticides (but not
pesticide intermediates) which are covered under FIFRA and for food,
drugs, cosmetics, and their intermediates, which are covered by FFDCA.
While other uses could potentially be subject to TSCA, EPA has not at
this time been able to identify viruses of macroorganisms in uses that
might be subject to TSCA. EPA requests comments on whether there are
known uses of viruses of macroorganisms that would be subject to TSCA
and whether an intergeneric approach such as that used for phages would
be appropriate for the viruses of macroorganisms. Comment is also
requested on whether EPA's approach for oversight of phages under TSCA
section 5 is appropriate.
B. Listing Microorganisms on the Inventory
This Unit describes how EPA proposes to explicitly list
microorganisms on the TSCA Inventory after MCAN review and the
rationale for the proposed listing.
1. The components of explicit listing. EPA proposes 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. EPA expects that this information would be a portion of the
information included in MCAN submissions.
a. Taxonomic designation. The taxonomic designations to the strain
level, as appropriate, would be provided for the recipient
microorganism and the donor(s) of the introduced genetic material.
Taxonomic designations may be those assigned by individual submitters
or by a culture collection. The designations would be substantiated by
a letter from a culture collection verifying the designation, by
literature references, or by the results of tests conducted for the
purpose of taxonomic classification. Upon request, the data supporting
the taxonomic designation should be provided to EPA. Where possible,
the genetic history of the recipient microorganism should be documented
back to the isolate from which it was derived.
b. Supplemental information. Many taxonomic designations at the
species level define phenotypically and genotypically diverse groups of
microorganisms. Therefore, supplemental information will be used to
identify as precisely as possible a specific microorganism on the
Inventory. Information on phenotypic and genotypic traits is necessary
only to the extent that it assists in the specific identification of
the reported microorganism.
(i) Phenotypic traits. This information concerns the
characteristics that reflect the interaction of a microorganism's
genotype and the environment in which it is intended to be used. For
example, information on intentionally added biochemical and
physiological traits is pertinent, since these traits may affect the
behavior and fate of a microorganism in the environment. Where
possible, submitters should prioritize phenotypic traits in order of
those likely to significantly change the microorganism's behavior and
thus its potential risk. Such important phenotypic changes may include
a change from asporogeny to spore-forming, an increase in the amount of
a specific product for which the microorganism is being used as an
intermediate, or the activation of a previously inactive enzyme that is
known to have negative human health or ecological effects.
(ii) Genotypic traits. This information concerns the distinguishing
genotypic characteristics of a microorganism, including the identity of
the genetic material that is introduced into the recipient
microorganism and the methods used to construct the reported
microorganism. For example, information on the vector construct,
cellular location, and number of copies of the introduced genetic
material is pertinent, since the vector may add genetic material and
traits, and the microorganism's phenotypic traits may be affected by
the number of copies and location of the introduced genetic material.
c. Deposit in a culture collection. Because microorganisms are
complex substances and because of the nature of the differences that
will be used to distinguish between similar organisms (isolates), EPA
is considering requiring that microorganisms listed on the Inventory be
deposited in a recognized culture collection. Deposited microorganisms
could serve as references for determining whether a related, unreported
microorganism, or a subsequently modified, inventoried microorganism is
the same as one already listed on the Inventory. Comments on this
proposal and alternative suggestions of how to distinguish among
closely related microorganisms are requested.
2. Inventory status of similar and subsequently modified
microorganisms. Since publication of the 1986 Policy Statement, EPA has
reviewed several intergeneric microorganism PMNs for general commercial
use. As discussed previously, the Agency has received an NOC for most
of these microorganisms, and these are listed on the TSCA Inventory.
The Agency recognizes that subsequent to listing a microorganism on the
Inventory, original submitters may make modifications to the genetic
material of the inventoried microorganism or companies other than the
original submitter may construct microorganisms which may be equivalent
to inventoried microorganisms. Questions would arise as to whether the
modified microorganism is equivalent to the microorganism listed on the
Inventory. At this time, EPA has concluded that no a priori guidance
can be given for determining whether a similar strain will be
equivalent to one listed on the Inventory. Manufacturers, producers, or
importers should consult with EPA concerning the status of their
microorganisms, as discussed in Unit II.B.1. of this preamble.
In making its decision on an individual microorganism, EPA will
consider the phenotype of the inventoried microorganism and assess how
the subsequent modifications will affect that phenotype. For example,
EPA believes that a MCAN may not be required when an inventoried
microorganism has undergone certain subsequent modifications of genetic
material where these modifications would not be likely to significantly
change the microorganism's behavior. The BSAC Subcommittee which met on
July 22, 1991, suggested that EPA continue to make these decisions on a
case-by-case basis, at least until EPA gains more experience. Although
EPA will make its decisions on a case-by-case basis, microorganisms
that may be judged by EPA to be equivalent to inventoried
microorganisms include those that have experienced deletions,
rearrangements, amplifications, point mutations, and/or plasmid loss
within a single genome, either spontaneously or through use of chemical
or physical mutagens. The Agency recognizes that deletions,
rearrangements, amplifications, point mutations, and plasmid loss could
occur spontaneously in any microorganism maintained in pure culture, in
response to stresses such as freezing or thawing, or as a result of
mistakes made during the microorganism's replication of its genetic
material.
EPA recommends that potential submitters consult the Agency for
clarification of their reporting obligations whenever additional
changes are made to inventoried microorganisms. The Agency has reviewed
several bona fide submissions and has determined on a case-by-case
basis that the microorganisms described were equivalent to previous PMN
submissions. In one case, the microorganism which was the subject of
the bona fide submission was derived from the same strain as the
inventoried microorganism using similar methods, and intrageneric
material encoding the same enzyme function was introduced. Although a
small number of base pairs in the intrageneric material had been
genetically altered, no new trait was introduced into the bona fide
microorganism compared to the inventoried microorganism. In a separate
case, the bona fide microorganism contained genetically modified
intrageneric material encoding the same function introduced into the
inventoried microorganism as well as a small fragment of non-coding,
non-regulatory intergeneric genetic material that had been derived from
the same source as that introduced into the inventoried microorganism.
Although a small number of base pairs had been altered in this
intergeneric material, no new trait was present in the bona fide
microorganism compared to the inventoried microorganism.
3. Identification of microorganisms currently listed on the
Inventory. EPA wishes to provide manufacturers and processors who are
using microorganisms which were listed on the Inventory prior to the
1986 Policy Statement the opportunity to provide information for a
specific, explicit listing, if necessary. In 1978, when EPA compiled
its initial TSCA Inventory, 192 microorganisms were reported. These
microorganisms are currently described on the Inventory by taxonomic
designations only, without any supplemental information describing how
they were made. They are listed in the 1985 Edition, Volume V, of the
TSCA Inventory. The list of microorganisms is included in the docket
for this rulemaking. The list may be obtained upon request at the
address included in the FOR FURTHER INFORMATION CONTACT section of this
preamble. EPA believes that most, if not all, of the 192 microorganisms
would not be considered new under this proposed rule, since the
listings appear to describe microorganisms which are not intergeneric.
Thus, these microorganisms would be implicitly included on the
Inventory and may continue to be manufactured for general commercial
use.
However, EPA wishes to ensure that all listed microorganisms are
described in a consistent manner. Accordingly, EPA advises
manufacturers and importers of any of the 192 listed microorganisms to
inform EPA of their status under this proposed rule during the public
comment period. Any manufacturers of microorganisms that would be
considered new under any final rules will be given the opportunity to
provide information to EPA to ensure consistent listing of the
microorganisms on the Inventory. If EPA is not notified about a
microorganism, the Agency will assume it would be implicitly included
because it is not intergeneric, and it will be removed from the
Inventory list as an explicit listing under EPA's TSCA section 8(b)
authority.
As discussed previously, EPA has reviewed a number of intergeneric
microorganism PMNs under the 1986 Policy Statement and has listed the
microorganisms on the Inventory. These microorganisms will be retained
on the Inventory if the proposal becomes final. If changes are made
which require alteration of Inventory listings, EPA will announce them
in the Federal Register.
C. SNUR Process
EPA is not proposing any significant new use rules (SNURs) in this
document. Instead, EPA is proposing, in subpart L of part 725,
procedures to enable it to issue SNURs in the future. Microorganisms
subject to SNUR reporting would be listed in proposed subpart M of part
725. This Unit discusses the SNUR process that EPA is proposing. This
process is adapted from the process in place for traditional chemicals
in part 721 with only slight modifications.
1. SNURs applied to microorganisms. Although EPA is not proposing
SNURs for any microorganisms in this document, it is conceivable that,
in the future, certain specific uses of microorganisms may raise
concerns for human health or the environment. Because the behavior of a
specific microorganism is influenced by the environment into which it
is introduced (Refs. 5, 7, 8, and 9), it may be necessary to evaluate
the risk of some microorganisms when the environment of use is changed.
For example, EPA was asked whether any uses of ``Ice +'' strains of
Pseudomonas syringae might be subject to SNUR reporting. At the time,
the ``Ice +'' microorganism was being used for snowmaking at ski
resorts. In that situation, EPA decided that terrestrial uses of the
microorganism for such activities as snowmaking at ski resorts,
icemaking at ice skating rinks, commercial air conditioning, and spray-
ice construction applications did not pose significantly different
exposures and therefore would not require SNUR reporting to EPA.
However, EPA did indicate that because use of the microorganism for
cloudseeding would present a significantly different exposure scenario
than the terrestrial uses, EPA might require SNUR reporting prior to
use of the live microorganism for cloudseeding. In such cases, EPA
believes it may be appropriate to use SNUR authority to monitor the
commercial development of these substances so that EPA can be apprised
of significant increases in exposure potential or significant changes
in exposure patterns. These significant increases may warrant control
measures or testing. As noted earlier, the MCAN submission and review
process will be used for microorganisms subject to SNUR reporting.
2. Expedited process for issuing SNURs. If EPA finds it necessary
to issue SNURs for new microorganisms reviewed under the MCAN process,
EPA will use, when appropriate, expedited procedures based on those
established in part 721, subpart D. The procedures for issuing
expedited SNURs for microorganisms are set forth in proposed
Sec. 725.980. EPA is not soliciting separate public comment on these
procedures, since they have already been adopted by EPA. This section
relies on the rationale originally stated in the Federal Register
notices establishing the expedited SNUR process for other new
substances under part 721. The SNUR procedures are discussed here and
included in the regulatory text for completeness, so that the public
will understand all the regulatory provisions potentially applicable to
microorganisms.
A limited amount of toxicity data is typically submitted with
premanufacture notifications (PMNs) for chemical substances. Thus, EPA
often bases its reviews on structure-activity relationships (SARs).
MCANs are expected to present similar problems in data gaps, since
current knowledge of microbial ecology is limited, and microorganisms
subject to TSCA are expected to be used in an ever-expanding variety of
applications and thus a multitude of different exposures. Should the
Agency determine it does not possess sufficient information to make a
risk judgement, EPA could find under TSCA section 5(e) that it had
insufficient information to determine whether the new microorganism
presents an unreasonable risk of injury to health or the environment.
In most such cases, EPA believes that it is appropriate to negotiate a
consent order under section 5(e) with the notice submitter to control
human exposure and/or environmental releases until test data or other
information sufficient to assess adequately the potential hazard become
available. Current experience indicates that section 5(e) consent
orders for traditional chemicals have specified a variety of control
measures. For microorganisms, EPA may place restrictions on site
location or size, production volume or method of application, field or
laboratory containment procedures, routine or emergency mitigation
procedures, or testing procedures.
Section 5(e) orders are binding on the original notice submitter
but do not apply to other manufacturers of the same microorganism.
Without additional regulation, other persons can manufacture, import,
or process the microorganism without EPA review and without the
restrictions imposed on the original MCAN submitter by the section 5(e)
order. To limit all manufacturers equally, EPA imposes SNURs.
Currently, EPA uses its SNUR authority to extend limitations in
section 5(e) orders to other manufacturers, importers, and processors
of chemical substances. This ensures that the original submitter and
subsequent manufacturers, importers, and processors are treated in an
equivalent manner. SNURs are framed so that noncompliance with the
control measures or other restrictions is defined as a ``significant
new use.'' Thus, other manufacturers, importers, and processors of the
substances must either observe the SNUR restrictions or submit a notice
to EPA at least 90 days before initiating activities that deviate from
these restrictions. After receiving and reviewing such a notice, EPA
would have the option of either permitting the new use or acting under
section 5(e) or (f) to regulate the new submitter's activities. EPA
intends to use this same process for microorganisms. In addition to
assuring that all manufacturers, importers, and processors are subject
to similar reporting requirements and restrictions, expedited SNURs
assure that EPA would have an opportunity to review and evaluate data
and, when necessary, regulate prospective manufacturers, importers, or
processors of a listed microorganism before a significant new use of
that microorganism occurs.
D. Confidential Business Information
EPA's confidential business information (CBI) policy is designed to
provide effective public participation by making meaningful information
available. In developing confidentiality provisions for submissions,
EPA has balanced the need to provide nonconfidential information to the
public in a reasonable period of time, to obtain the information it
needs to respond to FOIA requests, and to allow persons to assert CBI
claims with the minimum burden. In developing its position for this
rulemaking, EPA has considered its experience reviewing PMNs for
traditional chemicals and microorganisms and comments received on its
February 1989 FR notice. This Unit discusses the requirements proposed
in subpart C of part 725 and the rationale for EPA's proposal.
1. Assertion of CBI claims. A person may assert a claim of
confidentiality for any information submitted to EPA, with certain
exceptions. However, submitters are encouraged to minimize the amount
of CBI in biotechnology submissions, so that the public may participate
as fully as possible in the review process. All CBI claims must be
asserted at the time of submission of the information.
2. Generic information. Submitters who claim microorganism identity
and/or use as CBI also must provide generic information for release to
the public. By requiring generic identity and use information, EPA
would meet its obligation to provide the public with important
information related to the potential risks of new microorganisms
without revealing CBI. EPA needs this information to prepare Federal
Register notices to announce EPA's receipt of submissions or EPA's
decisions regarding exemption requests.
The generic designations must reveal the identity and use of the
microorganism to the maximum extent possible without revealing
proprietary information. Submitters are encouraged to review EPA's
``Guidelines for the Preparation of Generic Descriptions of
Confidential Microorganism Identity and Use'' and consult with EPA
regarding appropriate generic information prior to submitting a notice.
The guidelines are available from EPA's Environmental Assistance
Division (see FOR FURTHER INFORMATION CONTACT Unit). Microorganism
identity must be specific enough to allow clear interpretation of any
accompanying health and safety data. When the location of the release
site is claimed as CBI, a generic description for use must include
information regarding the type of environment into which the
microorganism will be released.
3. Identity in health and safety studies. TSCA section 14(b) states
that EPA is not prohibited from disclosing health and safety studies of
substances for which TSCA section 5 notification is required, unless
disclosure reveals confidential information on process or mixture.
Historically, the Agency has considered specific chemical identity to
be part of a health and safety study, even when it does not appear in
the study. However, during the development of the PMN rule, industry
expressed substantial concern about the harm of disclosing confidential
chemical identities. At that time EPA explored ways of limiting the
commercial harm of such disclosure while still meeting the requirements
of TSCA section 14(b) and providing the public with adequate
information about health and safety studies. The CBI requirements in
the final PMN rule reflected EPA's desire to balance these needs (48 FR
21722, May 13, 1983).
EPA has determined that the regulations developed to address
chemical identity in health and safety studies can also be applied to
microorganism identity. In this regard, if any health and safety
information has been submitted for the microorganism in question, the
specific microorganism identity will be held confidential only if
disclosure would reveal confidential process or mixture information or
if the specific microorganism identity is not necessary to interpret
any of the information.
Under this approach, companies that claim specific microorganism
identity confidential in their submissions and wish to argue that
knowledge of the specific identity is not necessary to interpret their
health and safety information are encouraged to choose generic names
which are sufficiently specific to allow interpretation of such
information. Sufficiently specific generic names will tend to support
arguments that disclosure of the specific microorganism identity is not
necessary to understand the health and safety information.
4. Current policy for substantiation of CBI claims. EPA currently
requires submitters of all PMNs for new microorganisms to be released
to the environment to substantiate confidentiality claims at the time
of submission. This includes PMNs for environmental releases of new
microorganisms for R&D as well as for general commercial use, but it
does not require upfront substantiation of CBI claims in PMNs for
closed system uses of new microorganisms. This policy will continue in
effect, until a final rule is promulgated for microorganisms. Like the
chemicals program, EPA requires that CBI claims in NOCs for
microorganisms be reasserted and resubstantiated when the NOC is
submitted.
5. Proposed changes for substantiation of CBI claims--a.
Submissions for general commercial uses of microorganisms. To balance
the competing needs of opening the review of submissions for
microorganisms to public scrutiny and participation while protecting
legitimate CBI claims, EPA proposes to require upfront substantiation
of CBI claims in all submissions for general commercial uses of
microorganisms. EPA will not distinguish between closed system uses and
other uses of microorganisms. Anyone submitting a MCAN, a TME, or a
Tier II exemption request will be required to substantiate CBI claims
at the time of submission. Failure to include substantiation of any CBI
claims, by submitting written answers to the questions, will render the
submission incomplete; and it will be returned to the submitter.
EPA believes that the upfront substantiation requirement for CBI
claims will impose little burden on submitters of MCANs, TMEs, and Tier
II exemption requests. Because MCAN, TME, and Tier II exemption request
submitters are ready to put their products on the market, they 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.
b. TERA submission. With respect to upfront substantiation for
TERAs, EPA is proposing two options and asking for public comments on
both. In comments in response to the 1989 FR notice, industry groups
raised the issue of adequate protection for R&D. Pointing out that R&D
activities involving microorganisms will be facing regulatory burdens
that are not imposed on chemical R&D, industry groups said that
additional burdens combined with insufficient CBI protection at the R&D
stage could reduce incentives to innovate. While submitters are
particularly concerned about protecting information at the R&D stage,
the public is most interested in participating in the reviews of the
first environmental releases of new microorganisms. Public interest
groups commented that upfront substantiation is essential to allow
public access to information in time to participate in reviews. Because
EPA recognizes the importance of the interests of both parties, EPA is
asking for additional comments on how best to resolve this issue for
CBI claims in TERAs.
(i) Option 1: Require upfront substantiation of all CBI claims in
TERAs. EPA is aware that industry believes that this requirement
imposes a greater burden on R&D submitters than is necessary.
Experience gained by continuing to require upfront substantiation of
CBI claims in submissions for R&D activities will help EPA determine
whether this requirement improves public access to information. In the
meantime, EPA specifically requests comment on how the burden to
submitters could be minimized if upfront substantiation of CBI claims
in TERAs is promulgated as part of the final rule.
(ii) Option 2: Do not require upfront substantiation of CBI claims
in TERAs. The second option is to adopt the current requirements for
chemical PMNs, that is, require CBI substantiation only after the
receipt of a FOIA request. EPA is concerned that given the shorter
review period for TERAs, insufficient information may be made available
to the public if upfront substantiation of CBI claims is not required.
For this reason, EPA specifically requests comment on how public access
to information could be improved if submitters were not required to
provide upfront substantiation of CBI claims in TERAs.
c. Substantiation questions. EPA's general procedures for
processing and reviewing confidentiality claims are published at 40 CFR
part 2. The basic points that should be covered in CBI substantiation
are set out at 40 CFR Sec. 2.204(e)(4)(i) through (ix). To ensure that
substantiation responses are appropriate for submissions involving
microorganisms, EPA has developed a more specific set of questions
based on the points in 40 CFR part 2. These questions, which are
delineated in proposed Sec. 725.94, are designed to reduce the burden
of substantiation by focussing the inquiry on points relevant to a
biotechnology product.
E. User Fees
Section 26(b) of TSCA provides that EPA may by rule establish fees
for persons required to submit data under section 4 or 5 to defray the
costs of administering TSCA. EPA must take into account the submitter's
ability to pay the fee and the cost of reviewing the submitted data.
EPA is using this authority to collect fees for notices submitted on
microorganisms.
EPA regulations already require persons to remit fees to EPA when a
PMN or SNUN is submitted to the Agency for review (40 CFR Sec. 700.45).
For MCAN submissions, EPA is proposing to amend part 700 to establish a
fee of $100 for notifications submitted by small businesses, and $2,500
for all other businesses. For purposes of this proposed rule, small
businesses are defined as companies with total annual sales of less
than $40 million. These proposed fees for MCANs are the same as those
set for submissions of PMNs for other chemical substances. EPA believes
that its costs of reviewing MCAN notifications will equal or exceed the
cost of reviewing PMNs for other chemical substances.
EPA is not proposing user fees for other submissions under this
proposed rule, including TERAs and Tier II exemption requests. EPA is
not reopening the general issues applicable to the adoption of user
fees for comment in this document, since comments on the subject were
addressed in a final rule published in the Federal Register of August
17, 1988 (53 FR 31248).
F. Section 8(e) Reporting Requirements
Any person who manufactures, imports, processes, or distributes in
commerce a TSCA-covered microorganism, whether new or existing, and/or
product(s) therefrom (including a person engaged solely in R&D) is
reminded about the statutory responsibility to immediately report to
EPA any information the person obtains which reasonably supports the
conclusion that such microorganism, or a product therefrom, presents a
substantial risk of injury to health or the environment, unless the
person has actual knowledge that EPA has been adequately informed
already about the information. Guidance regarding the section 8(e)
reporting requirement is provided in EPA's section 8(e) policy
statement (``Statement of Interpretation and Enforcement Policy;
Notification of Substantial Risk'' 43 FR 11110; March 16, 1978) and its
technical amendment (52 FR 20083; May 29, 1987). Additional information
regarding TSCA section 8(e) reporting is provided in 56 FR 4128
(February 1, 1991); 56 FR 19514 (April 26, 1991); 56 FR 28458 (June 20,
1991); and 56 FR 49478 (September 30, 1991).
Should EPA receive a section 8(e) substantial risk notice with
respect to the manufacture, importation, processing or distribution in
commerce of a microorganism, EPA may proceed to regulate the activity
causing the risk. If EPA determines, under authority of TSCA section 7,
that the activity or microorganism, including its parts or products, on
which a section 8(e) notice was received, is ``imminently hazardous''
to health or the environment, EPA may require immediate suspension of
manufacturing, processing or distribution in commerce of the imminently
hazardous microorganism. EPA also may require any remediation necessary
to obtain permanent relief as may be necessary to protect health or the
environment from the unreasonable risks associated with the
microorganism. This authority applies to any ``imminently hazardous''
microorganism or its parts or products, regardless of whether the
microorganism is used for R&D or manufactured for general commercial
use.
The term ``imminently hazardous chemical substance or mixture'' in
TSCA section 7 means a chemical substance or mixture which presents an
imminent and unreasonable risk of serious or widespread injury to
health or the environment. Such a risk is considered imminent if the
manufacture, processing, distribution in commerce, use or disposal of
the substance is likely to result in such injury before a final rule
can be issued under TSCA section 6.
G. Export Notification and State Preemption
This Unit discusses two other provisions of TSCA concerning export
notification and Federal preemption that may be of some concern to the
public in implementing this proposed rule.
1. General. Section 12 of TSCA generally provides that the Act does
not apply to chemical substances produced for export. However, section
12(b)(2) requires, in pertinent part, that EPA must be notified about
the export of any substance in U.S. production that is subject to a
rule, an order, or some other relief granted under section 5. EPA must
then notify the government of the receiving country. EPA's export
notification regulations are codified at 40 CFR part 707.
Section 18(a) provides that TSCA generally does not preempt the
authority of any State or local government to regulate a chemical
substance. There are some exceptions, however. In particular, section
18(b) states that, if EPA issues a rule or order under section 5
``which is applicable to a chemical substance'' and ``which is designed
to protect against a risk of injury...associated with such substance'',
no State or local government may issue or continue in effect any
requirement designed to protect against the same risk, with certain
exceptions. The exceptions are that the State or local requirement may
be identical to the Federal requirement, may be issued under authority
of another Federal law, or may prohibit use of the substance (other
than in the manufacture or processing of another chemical substance or
mixture).
2. Applicability. EPA interprets the exemption of section 12(a) to
apply only to those microorganisms manufactured, processed, or
distributed solely for export. If the microorganism is manufactured,
processed, or distributed for any use in the United States, it is
subject to TSCA (see TSCA section 12(a)(1)(A)). Thus, any R&D in the
U.S. is subject to applicable regulations, as are any other activities
involving a microorganism that are described in this proposed rule.
Similarly, any release of microorganisms to the environment prior to
export will not be considered solely for export and is therefore
subject to applicable regulations.
Since the rules proposed in this document are either of general
applicability and largely procedural, or are exemptions from regulation
and only establish procedures to screen against potential risk, neither
section 12(b) export notification nor section 18(b) preemption applies
at this time.
Sections 12(b) and 18(b) would apply should EPA decide to take
regulatory action against a microorganism or class of microorganisms,
for example, by issuing an order under TSCA section 5(e). In such
cases, section 12(b) export notification would apply automatically.
While preemption under section 18(b) would apply by operation of
statute, in individual cases EPA could issue rules that specifically
require compliance with applicable State or local requirements.
H. Regulatory Text Overview
The regulatory text comprises the language which EPA is proposing
to incorporate into the Code of Federal Regulations (CFR). While the
preamble to this proposed rule provides the rationale for EPA's
preferred approach towards the oversight of certain activities
involving new microorganisms, the regulatory text includes all the
proposed requirements to which the regulated community would be
subject.
The regulatory text 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 proposed rule. Additional
amendments to parts 720, 721, and 723 consolidate TSCA section 5 review
of microorganisms into part 725.
EPA is proposing to establish a new part 725 of Title 40 of the
CFR. EPA believes that consolidating all requirements and procedures
applicable to new microorganisms into one part of the CFR is justified
because of the differences between microorganisms and other chemical
substances.
The consolidation will benefit the public by providing greater
clarity. Part 725 is devoted exclusively to the review of
microorganisms under section 5 of TSCA and is currently divided into
eight subparts. Subparts A, B, and C consolidate provisions primarily
adapted from parts 720 and 721. Subpart A, which includes definitions
that are applicable throughout part 725, describes general provisions
and applicability. Subpart B describes administrative procedures that
are applicable to all submissions under part 725. Subpart C describes
confidentiality provisions that are applicable to all submissions under
part 725.
Subpart D, which combines the general PMN and SNUN requirements
adapted from parts 720 and 721, describes the reporting requirements
and review process pertaining to MCANs. Subparts E, F, and G describe
the reporting requirements and review processes for applications for
exemptions from full MCAN reporting. Subpart E, which is almost
entirely new, describes who is eligible to submit a TERA or receive a
TERA list exemption, and what criteria must be met to receive an
exemption from EPA review for certain types of R&D activities. Subpart
F, which is an adaptation of Sec. 720.38, describes the requirements
for a test marketing exemption for microorganisms. Subpart G, which is
entirely new, describes what criteria must be met in order to qualify
for Tier I or Tier II exemptions for certain microorganisms in general
commercial use. Subpart L, which is adapted from part 721, describes
additional procedures for reporting significant new uses of
microorganisms. Although significant new use rules are not being
proposed at this time, it is intended that subpart M will list
microorganisms and specific significant new uses when they are
promulgated.
I. Rulemaking Process and Public Hearings
EPA is conducting this rulemaking under notice and comment
rulemaking procedures. Interested persons have the opportunity to
submit written comments to the address identified under the ADDRESSES
Unit of this preamble. EPA will carefully consider all such comments.
EPA is also providing an opportunity for an informal public hearing
on the proposed rule. This hearing will be held only if EPA receives a
timely written request for such a hearing.
As a general matter, EPA is not required to hold a public hearing
in informal notice and comment rulemaking of this type. However, use of
section 5(h)(4) modifies the general rulemaking requirements by
referencing TSCA section 6(c)(2) and (3) rulemaking procedures. Under
those procedures, EPA must hold an informal public hearing, if
requested, and, if properly requested and granted by EPA, allow an
opportunity to present rebuttal submissions and conduct cross-
examinations related to disputed issues of material fact.
EPA does not anticipate that, even if a hearing is held, there will
be a need for rebuttal submissions and crossexamination, because the
section 5(h)(4) portion of this proposed rulemaking is based primarily
on matters of science policy that do not yield disputed factual issues.
V. Economic Impact and Regulatory Flexibility Analysis
A. Regulatory Impact Analysis
1. 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 the proposed
rule. Though direct regulatory costs attributable to the proposed rule
were not estimated to be in excess of $100 million annually, EPA has
designated the rule as ``significant'' under Executive Order 12866
because it raises novel policy issues arising out of legal mandates.
This unit presents a summary of the RIA's key findings and estimates.
2. Characteristics of the 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 proposed 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 proposal is believed to
represent only a small portion of reported sales. EPA also estimates
that approximately 300 universities could be affected by the
rulemaking.
3. Costs to potential submitters. Due to data limitations and the
uncertainties associated with projecting future product development
activities in biotechnology application areas subject to the proposed
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. Estimates are believed to represent a
reasonable approximation of actual costs attributable to the rule.
In assessing the potential cost impact of the proposed rule, EPA
focussed on two impact years, the first and fifth years following the
time of proposal (assumed to be 1992 and 1996, for the purposes of
analysis). This approach was used because of the relative immaturity of
the biotechnology sectors potentially subject to the proposed rule and
the difficulty in attempting to forecast long-term technological and
marketing developments. However, EPA wishes to emphasize that estimated
costs could be significantly higher in the long-term, owing to industry
growth.
Four major cost areas were identified, based on an analysis of the
requirements of the proposed 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
confidential business information (CBI) claims; and one-time costs
attributable to rule familiarization.
Incremental costs to industry (industry-wide costs excluding
requirements under current policy) were estimated to fall between
$890,000 and $2.2 million in year 1 and between $56,000 and $460,000 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.
Cost impacts on individual products will vary, depending on
application area. Submitters qualifying for exemptions in connection
with microorganisms intended for general commercial use will realize
net savings relative to current reporting requirements. On the other
hand, submitters reporting R&D activities involving environmental
release may realize an increase in regulatory burden under the proposed
rule.
4. Costs to the Federal government. EPA estimated the potential
costs to government associated with the proposed 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 submission.
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 would be 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 to fall between
$115,000 and $122,000 in year 1, while a net savings to EPA, estimated
to fall between $39,000 and $184,000, is expected in year 5. These
savings arise in connection with the substantial number of full reviews
that will be avoided if the exemption provisions of the proposed rule
are promulgated.
5. Benefits of the proposed 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 microorganisms. 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 proposed rule
would be marginal, as these requirements are based on current policy.
However, the proposed 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 proposed rule, since
reporting in connection with field experiments has been voluntary since
1986. Although the Agency has been receiving voluntary submissions, EPA
is not certain whether this practice is universal or whether those
filing voluntarily would continue to do so in the absence of this
proposed rule.
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 proposed rule's potential
impact on the pace of product development. A more certain regulatory
climate could stimulate business activity, as could a more reassured
public. The proposed 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 could hamper competition.
6. Effects of the proposed rule on innovative activity. As a result
of the proposed 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. These factors are
expected to be highly variable and product-specific.
7. Impacts on small business. EPA survey data suggest that 42
percent of companies potentially affected by the proposed 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 develop options to
provide relief to such businesses. The options considered include
reducing CBI substantiation requirements and the elimination of the
$100 filing fee.
B. Request for Comment on Economic Issues
Based on the analysis presented in the RIA, EPA's preliminary
findings are that this proposed rule should not adversely affect either
innovation or international competitiveness in biotechnology; to the
contrary, EPA believes that this proposed rule will provide needed
regulatory and procedural clarity under TSCA to enable the U.S.
biotechnology industry to commercialize products while ensuring
appropriate oversight to protect public health and the environment.
EPA nevertheless believes that this proposed rule should continue
to be evaluated in light of its potential impact on innovation and
international competitiveness. To this end, the Agency is requesting
public comment regarding the economic impacts associated with this
proposed rule. Data or other information are specifically requested in
connection with the following: rate of capital acquisition and critical
factors affecting R&D capitalization; rate and magnitude of R&D
expenditures; data regarding actual submissions under the current
policy, e.g., project development costs, regulatory burdens,
development schedules and revenues.
VI. Rulemaking Record and Electronic Availability of Documents
A record has been established for this proposed rule under docket
number ``OPPTS-00049C.'' A public version of this record which does not
include any information claimed as CBI (see Unit VII. of this
preamble), is available for inspection from noon to 4 p.m., Monday
through Friday, excluding legal holidays. The public record is located
in the TSCA Nonconfidential Information Center (NCIC) (also known as
the TSCA Public Docket Office), Rm. NE-B607, 401 M St., SW.,
Washington, DC 20460.
As part of an interagency ``streamlining'' initiative, EPA is
making this proposed rule and certain support documents available
electronically. They may be accessed through the Internet at:
gopher.epa.gov.
EPA is very interested in learning whether persons have obtained
these documents electronically and what their experiences were in doing
so. Persons who comment on this proposed rule are encouraged to provide
feedback on this electronic availability with their comments.
To obtain further information or to provide feedback on the
electronic availability of these documents, please contact Juanita Geer
(Telephone: 202-260-1532; FAX: 202-260-1657; Internet:
[email protected]). Please be advised that Ms. Geer will
accept only feedback on the electronic availability of these documents;
all comments on the substance of the proposed rule must be submitted to
the docket above.
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 proposed rule. 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 this proposed rule.
5. The Regulatory Impact Analysis for this proposed rule.
6. Support documents and reports.
7. Records of all communications between EPA personnel and persons
outside EPA pertaining to the development of this proposed 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.
EPA will accept additional materials for inclusion in the record at
any time between the date of publication of this proposed rule and the
designation of the complete record. EPA will identify the complete
rulemaking record by the date of promulgation of the final rule.
Comments received on this proposed rule, along with a complete
Index of the docket for this rulemaking, is available to the public for
inspection from noon to 4 p.m., Monday through Friday, except legal
holidays, in the TSCA Nonconfidential Information Center, Rm. NE-102,
401 M St., SW., Washington, DC 20460. Only nonconfidential versions of
documents are included in the public record.
VIII. References
The following books, articles, and reports were used in preparing
this notice and were cited in this notice by the number indicated
below:
(1) U.S. Congress, Office of Technology Assessment. 1988. ``New
Developments in Biotechnology - Field-Testing Engineered Organisms:
Genetic and Ecological Issues'', OTA-BA-350. U.S. Government Printing
Office, Washington, DC.
(2) U.S. Congress, Subcommittee on Investigations and Oversight,
House Science, Space and Technology Committee. 1986. ``Issues in the
Federal Regulation of Biotechnology: from Research to Releases.''
Washington, DC.
(3) U.S. Environmental Protection Agency, Office of General
Counsel, Pesticides and Toxic Substances Division. 1983. ``Status of
recombinant DNA and new life forms under Toxic Substances Control Act
(TSCA). Washington, DC.
(4) U.S. Congress, Office of Technology Assessment, ``New
Developments in Biotechnology - U.S. Investment in Biotechnology
Summary,'' Vol. 4, p. 13. OTA-BA-401, U.S. Government Printing Office,
Washington, DC.
(5) Tiedje, J., Colwell, R.K., Grossman, Y.L., Hodson, R.E.,
Lenski, R.E., Mack, R.N., Regal, P.J. 1989. ``The planned introduction
of genetically engineered organisms: Ecological considerations and
recommendations.'' Ecology 70(2):298-315.
(6) Schroth, M.N. 1983 ``Bacteria as biocontrol agents of plant
disease.'' Pages 362-369 in Klug, M.J. Reddy, C.A., eds. Current
Perspectives in Microbial Ecology. American Society for Microbiology,
Washington, DC.
(7) Dunigan, E.P., Bollich, P.K., Hutchinson, R.L., Hicks, P.M.,
Zaunbrecher, F.C., Scott, S.G., Mowers, R.P. 1984. ``Introduction and
survival of an inoculant strain of Rhizobium japonicum in soil.''
Agronomy Journal 76:463-466.
(8) Simberloff, D. 1986. ``Introduced insects: a biogeographic and
systematic perspective.'' Pages 4-26 in H.A. Mooney and J.A. Drake,
eds. Ecology of biological invasions of North America and Hawaii.
Ecological Studies 58. SpringerVerlag, New York.
(9) Salisbury, E. J. 1961. Weeds and Aliens. Collins, London.
(10) Baker, H. G. 1986. ``Patterns of plant invasion in North
America.'' Pages 44-57 in Mooney, H. A. and Drake, J. A., eds., Ecology
of Biological Invasions of North America and Hawaii, Ecological Studies
58. Springer-Verlag, New York.
(11) Gill, D.M. 1982. ``Bacterial toxins: a table of lethal
amounts.'' Microbiological Reviews 46(1): 86-94.
(12) Gill, D.M. 1987. ``Bacterial Toxins: description.'' Laskin,
A.I. Lechevalier, H.A., eds. Pages 3-18 in CRC Handbook of
Microbiology, 2nd edition, Volume VIII, Toxins Enzymes. CRC Press, Boca
Raton, FL.
(13) Sayre, P.G. and Miller, R.V. 1991. ``Bacterial mobile genetic
elements: Importance in assessing the environmental fate of genetically
engineered sequences.'' Plasmid 26:151-171.
(14) Kokjohn, T.A. 1989. ``Transduction: mechanism and potential
for gene transfer in the environment.'' Pages 73-97 in Levy, S.B. and
Miller, R.V., eds. Gene Transfer in the Environment. McGraw-Hill
Publishing Co., New York.
(15) Stotzky, G. 1989. ``Gene transfer among bacteria in soil.''
Pages 165-222 in Levy, S.B. and Miller, R.V., eds. Gene Transfer in the
Environment. McGraw-Hill Publishing Co., New York.
(16) Saye, D.J. Miller, R.V. 1989. ``The aquatic environment:
consideration of horizontal gene transmission in a diversified
habitat.'' Pages 223-259 in Levy, S.B. and Miller, R.V., eds. Gene
Transfer in the Environment. McGraw-Hill Publishing Co., New York.
(17) Jeffrey, W., Paul, J., and Stewart, G. 1990. ``Natural
transformation of a Marine Vibrio Species by Plasmid DNA.'' Microbial
Ecology 19:259-268.
(18) Lewin, B., ed. 1987. Pages 55-56 in ``Genes, Third Edition.''
John Wiley Sons, New York.
(19) Maki, H., Horiucki, T., and Sekiguchi, M. 1983. ``Structure
and expression of the DNAQ mutator and RNase H genes of Escherichia
coli: Overlap of the promoter regions.'' Proceedings of the National
Academy of Sciences 80:7137-7141.
(20) Ippen-Ihler, K. 1989. ``Bacterial Conjugation.'' Pages 33-72
in Levy, S.B. and Miller, R.V., eds. 1989. Gene Transfer in the
Environment. McGraw-Hill Publishing Co., New York.
(21) U.S. Environmental Protection Agency, Office of Toxic
Substances, Economics Technology Division, Chemical Engineering Branch.
1991. ``Analysis of environmental releases and occupational exposure in
support of proposed TSCA 5(h)(4) exemption.'' Washington, DC.
(22) Battelle. 1988. Final Report on Biosafety in Large-Scale rDNA
Processing Facilities. 6 volume set. U.S. EPA, Risk Reduction
Engineering Laboratory, Cincinnati, OH.
(23) National Institutes of Health, U.S. Department of Health Human
Services. 1984. ``Meeting of the Large-Scale Review Working Group of
the Recombinant DNA Advisory Committee.'' Recombinant DNA Bulletin
7(2): 68-74.
(24) Atlas, R. and Bartha, R. 1987. Microbial Ecology. Benjamin/
Cummings Publishing Company, Inc., Menlo Park, CA.
(25) Francki, R.I.B., Fauquet, C.M., Knudson, D.L., Brown, F.
(eds.) 1991. Archives of Virology/Supplementum 2. Springer-Verlag, NY.,
NY.
IX. Regulatory Assessment Requirements
A. Executive Order 12866
Under Executive Order 12866 (58 FR 51735, October 4, 1993), the
Agency must determine whether the regulatory action is ``significant''
and therefore subject to review by the Office of Management and Budget
(OMB) and the requirements of the Executive Order. Under section 3(f),
the order defines a ``significant regulatory action'' as an action that
is likely to result in a rule: (1) Having an annual effect on the
economy of $100 million or more, or adversely and materially affecting
a sector of the economy, productivity, competition, jobs, the
environment, public health or safety, or State, local or tribal
governments or communities (also referred to as ``economically
significant''); (2) creating serious inconsistency or otherwise
interfering with an action taken or planned by another agency; (3)
materially altering the budgetary impacts of entitlement, grants, user
fees, or loan programs or the rights and obligations of recipients
thereof; or (4) raising novel legal or policy issues arising out of
legal mandates, the President's priorities, or the principles set forth
in this Executive Order.
Pursuant to the terms of this Executive Order, EPA has determined
that this proposed rule is ``significant'' because it raises 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
Under the Regulatory Flexibility Act (5 U.S.C. 605(b)), EPA has
analyzed the economic impact of this proposed rule on small businesses.
A summary of this analysis appears in Unit V. of this preamble. This
proposed rule does not exempt small businesses. Preliminary analysis of
the impacts of this proposed rule on small businesses indicates that
the compliance costs may have a significant impact. Despite the
uncertainties and data gaps faced by EPA in developing this analysis,
EPA believes that it is prudent public policy to assume that the
requirements of the Regulatory Flexibility Act (Pub. L. 96-354) have
been triggered. EPA believes that review of certain new microorganisms
under TSCA is important to ensure that there are no unreasonable risks
to health and the environment, and that the mechanisms outlined in this
proposed rule will lessen impacts on small business as much as
possible.
The Regulatory Impact Analysis section on small business impacts
(Section VIII of the RIA, which is part of the public record for this
rulemaking) serves as the Initial Regulatory Flexibility Analysis
required by the Regulatory Flexibility Act. EPA intends to revise this
analysis prior to promulgation of the final rule. EPA requests comments
on the methodology employed in this analysis and the results of this
analysis.
C. Paperwork Reduction Act
The Office of Management and Budget (OMB) has approved the current
Premanufacture Notification and SNUR program under the provisions of
the Paperwork Reduction Act, 44 U.S.C. 3501 et seq. and has assigned
OMB control number 2070-0012. This proposed rule, when promulgated,
would modify those information collection requirements; an information
collection request addressing these modifications has been submitted to
OMB under the provisions of the Paperwork Reduction Act, 44 U.S.C. 3501
et seq.
Public reporting burden for this collection of information is
estimated to average 473 hours per response, including time for
reviewing instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing the
collection of information.
Send comments regarding the burden estimate or any other aspect of
this collection of information, including suggestions for reducing
burden, to Chief, Information Policy Branch, 2136, U.S. Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460, and to the
Office of Information and Regulatory Affairs, Office of Management and
Budget, Washington, DC 20503, marked ``Attention: Desk Officer for
EPA.'' The final rule will respond to any OMB or public comments on the
information collection requirements contained in this proposal.
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
Dated: August 19, 1994.
Carol M. Browner,
Administrator.
Therefore, it is proposed that 40 CFR Chapter I be amended as
follows:
PART 700--[AMENDED]
1. In part 700:
a. The authority citation for part 700 would continue 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 Sec. Sec. 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 TSCA.
* * * * *
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:
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 Sec. Sec. 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
Sec. Sec. 720.65(c) and 725.33 of this chapter.
PART 720 -- [AMENDED]
2. In part 720:
a. The authority citation for part 720 would continue 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 would continue 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 would continue to read as
follows:
Authority: 15 U.S.C. 2604.
b. In Sec. 723.50, by revising paragraph (a)(1) to read as follows:
Sec. 723.50 Chemical substances manufactured in quantities of 1,000
kilograms or less per year.
(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 of certain chemical substances manufactured in quantities
of 1,000 kilograms or less per year. This section does not apply to
microorganisms regulated under 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 regulated
under 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
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 regulated under 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.
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 this subpart.
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 report 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--Exemption for Microorganisms in General Commercial Use
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 Liability of the manufacturer or importer who uses 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 Applicable to Reporting on Significant
New Uses of Microorganisms
725.900 Scope and purpose.
725.910 Persons excluded from reporting of significant new uses.
725.912 Exemptions.
725.920 Exports and imports.
725.950 Additional recordkeeping requirements for reporting of
significant new uses.
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--[Reserved]
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 reporting requirements under section 5 of
TSCA for manufacturers, importers, and processors of microorganisms for
commercial purposes.
(b) TSCA section 5 covers chemical substances as defined under TSCA
section 3. Because EPA interprets the section 3 definition to include
microorganisms, section 5 also covers microorganisms. Unless otherwise
specifically stated in the Code of Federal Regulations, TSCA section 5
authority over microorganisms (as distinguished from other chemical
substances) will be implemented under this part.
(c) Microorganisms subject to reporting as new microorganisms will
be those which are intergeneric. In addition, any microorganism subject
to TSCA jurisdiction may be subject to reporting, if EPA determines by
rule that the microorganism is being manufactured, imported, or
processed for a significant new use.
(d) This subpart A describes the general organization for this part
and contains definitions generally applicable to this part.
(e) Subpart B of this part describes general administrative
procedures applicable to microorganisms subject to this part.
(f) Subpart C of this part establishes requirements for handling
confidential business information (CBI) and public access to
information submitted under this part.
(g) Subpart D of this part describes the persons and microorganisms
subject to Microorganism Commercial Activity Notices (MCANs),
prescribes the content of MCANs, and establishes procedures for
reviewing MCANs.
(h) Subpart E of this part establishes reporting requirements and
EPA review procedures for the TSCA Experimental Release Application
(TERA) for microorganisms intentionally tested in the environment
during commercial research and development activities. Subpart E of
this part also identifies microorganisms and classes of microorganisms
exempt from research and development reporting.
(i) Subpart F of this part establishes procedures for obtaining
test marketing exemptions (TMEs) for microorganisms.
(j) Subpart G of this part identifies microorganisms in general
commercial use under certain conditions of containment that are
eligible for Tier I and Tier II exemptions from subpart D reporting.
Subpart G of this part establishes reporting requirements and
procedures for expedited review of the Tier II exemption request.
(k) Subpart L of this part describes additional requirements
applicable to reporting on microorganisms subject to significant new
use rules under TSCA section 5(a)(2). All significant new uses of
microorganisms are subject to the MCAN requirements in subpart D of
this part.
(l) Subpart M of this part identifies specific significant new uses
of microorganisms subject to subpart D reporting.
Sec. 725.3 Definitions.
Definitions in section 3 of the Act (15 U.S.C. 2602), as well as
definitions contained in Sec. Sec. 704.3, 720.3, and 721.3 of this
chapter, apply to this part unless otherwise specified in this section.
In addition, the following definitions apply to this part:
Consolidated microbial commercial activity notice or consolidated
MCAN means any MCAN submitted to EPA that covers more than one
microorganism (each being assigned a separate MCAN number by EPA) as a
result of a prenotice agreement with EPA.
Containment and/or inactivation controls means any combination of
engineering, mechanical, procedural, or biological controls designed
and operated to restrict environmental release of viable microorganisms
from a structure.
Director means the Director of the EPA Office of Pollution
Prevention and Toxics.
Exemption request means any application submitted to EPA under
subparts E, F, or G of this part.
General commercial use means use for commercial purposes other than
research and development.
Genome means the sum total of chromosomal and extrachromosomal
genetic material of an isolate and any descendants derived under pure
culture conditions from that isolate.
Health and safety study of a microorganism or health and safety
study means any study of any effect of a microorganism or microbial
mixture on health or the environment or on both, including underlying
data and epidemiological studies, studies of occupational exposure to a
microorganism or microbial mixture, toxicological, clinical, and
ecological, or other studies of a microorganism or microbial mixture,
and any test performed under the Act. Microorganism identity is always
part of a health and safety study of a microorganism.
(1) It is intended that the term ``health and safety study of a
microorganism'' be interpreted broadly. Not only is information which
arises as a result of a formal, disciplined study included, but other
information relating to the effects of a microorganism or microbial
mixture on health or the environment is also included. Any data that
bear on the effects of a microorganism on health or the environment
would be included.
(2) Examples include:
(i) Tests for ecological or other environmental effects on
invertebrates, fish, or other animals, and plants, including: Acute
toxicity tests, chronic toxicity tests, critical life stage tests,
behavioral tests, algal growth tests, seed germination tests, plant
growth or damage tests, microbial function tests, bioconcentration or
bioaccumulation tests, and model ecosystem (microcosm) studies.
(ii) Long- and short-term tests of mutagenicity, carcinogenicity,
or teratogenicity; dermatoxicity; cumulative, additive, and synergistic
effects; and acute, subchronic, and chronic effects.
(iii) Assessments of human and environmental exposure, including
workplace exposure, and impacts of a particular microorganism or
microbial mixture on the environment, including surveys, tests, and
studies of: Survival and transport in air, water, and soil; ability to
exchange genetic material with other microorganisms, ability to
colonize human or animal guts, and ability to colonize plants.
(iv) Monitoring data, when they have been aggregated and analyzed
to measure the exposure of humans or the environment to a
microorganism.
(v) Any assessments of risk to health and the environment resulting
from the manufacture, processing, distribution in commerce, use, or
disposal of the microorganism.
Inactivation means that living microorganisms are rendered
nonviable. ``Introduced genetic material'' means genetic material that
is added to, and remains as a component of, the genome of the
recipient.
Intergeneric microorganism means a microorganism that is formed by
the deliberate combination of genetic material from organisms of
different taxonomic genera, including mobile genetic elements. The term
``intergeneric microorganism'' does not include a microorganism which
contains 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 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 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 TSCA
Inventory.
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 of this part, submitted to EPA in accordance with subpart E of
this part.
Well-characterized, non-coding regulatory region means a segment of
genetic material for which:
(1) The exact nucleotide base sequences of the regulatory region
and any inserted flanking nucleotides are known and documented.
(2) The regulatory region and any inserted flanking nucleotides do
not code for protein, peptide, or functional ribonucleic acid
molecules.
(3) 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.
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 of this part, are subject to the requirements of
this part.
(b) Microoganisms automatically included on the Inventory.
Microorganisms that are not intergeneric are automatically included on
the TSCA Inventory.
(c) Microorganisms not subject to this part. The following
microorganisms are not subject to this part, either because they are
not subject to TSCA jurisdiction or are not subject to reporting under
TSCA section 5.
(1) Any microorganism which would be excluded from the definition
of ``chemical substance'' in section 3 of TSCA and Sec. 720.3(e) of
this chapter.
(2) Any microbial mixture as defined in Sec. 725.3 of this part.
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 TSCA, 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 TSCA Inventory or the microorganisms and uses
specified in Sec. 725.239 or 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 or in
Sec. 725.239 or 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 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
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 a microorganism for commercial
purposes.
(iii) A description of research and development activities
conducted with the microorganism to date, demonstration of the
submitter's ability to produce or obtain the microorganism from a
foreign manufacturer, and the purpose for which the person will
manufacture, import, or process the microorganism.
(iv) An indication of whether a related microorganism was
previously reviewed by the Agency to the extent known by the submitter.
(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 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 subject to 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 subject to 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.
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:
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.
This statement must be signed and dated by an authorized official of
the submitter.
(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 theMCAN 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 (i) A person intends
to manufacture or import a new microorganism which is subject to the
notification requirements of this part, and (ii) 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
Sec. Sec. 725.150 through 725.160.
(b) Requirements specific to TERAs are described in
Sec. Sec. 725.250 through 725.260.
(c) Requirements specific to test marketing exemptions (TMEs) are
described in Sec. Sec. 725.350 and 725.355.
(d) Requirements specific to Tier I and Tier II exemptions for
certain general commercial uses are described in Sec. Sec. 725.424
through 725.460.
(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 the new
microorganism 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.
(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) Materially false or misleading statements. 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 TSCA 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 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, 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 or importer 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 files 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 files 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 TSCA section 5(h)(4), an exemption, in
whole or in part, from this part by sending a Letter of Application to
the Director, Chemical Control Division, Office of Pollution Prevention
and Toxics, U.S. Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460.
(2) 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.
(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 the Agency, 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 TSCA section 5(h)(4) exemption requires a determination that
there will be no unreasonable risk.
(i) An unreasonable risk determination under TSCA 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 Agency action to reduce that harm.
(ii) A determination of unreasonable risk under TSCA section
5(h)(4) 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.
(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, the claim(s) must be asserted by circling
the specific information which is claimed as confidential 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 information.
(i) One copy of the information 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.
(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.
(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. 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 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 human 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.
(i) If any information in such a submission is claimed as
confidential business information, the submitter must substantiate each
of those claims by submitting written answers to the questions in
paragraphs (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)(2)(i) of this section, the submission will be
considered incomplete and the TERA review period will not begin.
(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. 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 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 industry? 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:
(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 your
competitors.
(v) Patents.
(vi) Local, State, or Federal agency public files.
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.
(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 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: (i) Confidential process information, or (ii) information
unrelated to the effects of the microorganism on human 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 8 a.m. and noon
and 1 p.m. 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 TSCA 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.
(b) Persons subject to MCAN submission are described in
Sec. 725.105.
(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 Sec. Sec. 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 general
commercial use 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 (i) The manufacturer produces or processes the
microorganism exclusively for that person, and (ii) 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
general commercial use 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 general commercial use. 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 who
intend to use or distribute the microorganism 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 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 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
Sec. 725.25. 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 TSCA. The submitter must comply with any
applicable requirement of section 5(b) of TSCA.
(c) Contents of a MCAN. Each person who submits a MCAN under this
subpart must provide the information and test data described in
Sec. Sec. 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
provide EPA in writing with all information known to or reasonably
ascertainable by the person that would permit EPA to make a reasoned
evaluation of the human 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. However, no person is required
to include information which relates solely to exposure of humans or
ecological populations outside of the United States. The information to
be submitted under this subpart includes, but is not limited to, the
information listed in paragraphs (c) through (h) of this section. All
information submitted must be true and correct.
(b) When specific information is not submitted, an explanation of
why such information is not available or not applicable must be
included.
(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(s) and the new
microorganism. (i) Data substantiating the taxonomy of the recipient
microorganism(s) and the new microorganism(s) 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(s).
(iii) Other specific data by which the new microorganism(s) may be
uniquely identified for Inventory purposes.
(2) Genetic construction of the new microorganism(s). (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 data supporting the taxonomic designation.
(ii) Description of the traits for which the new microorganism(s)
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, function of the introduced
genetic material, including any changes predicted to alter function;
how the introduced genetic material is expected to affect behavior;
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(s).
(ii) Survival and dissemination under relevant environmental
conditions including a description of methods for detecting the
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(s).
(f) Total production volume. The estimated maximum amount of the
new microorganism(s) 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(s) 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(s) 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 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 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 to the
address listed in Sec. 725.25(c), as specified in paragraph (a)(3)(i)
of this section, 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 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 by 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 Sec. Sec. 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) Any person submitting a MCAN in response to the requirements of
this subpart shall not 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, general commercial use 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,
general commercial use begins on or after [insert date 44 days after
date of publication in the Federal Register of the final rule], 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, general commercial use
began or will begin before [insert date 44 days after date of
publication in the Federal Register of the final rule], the submitter
must submit the NOC by [insert date 44 days after date of publication
in the Federal Register of the final rule].
(3) Submission of an NOC prior to the commencement of manufacture
or import is a violation of TSCA section 15.
(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.
(c) Exemptions from part 725 are provided at Sec. Sec. 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 Sec. Sec. 725.255
and 725.260.
(f) EPA review procedures specific for TERAs are set forth in
Sec. Sec. 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) Certain research and development activities involving
microorganisms subject to TSCA jurisdiction are exempt from reporting
under this part. A person conducting research and development
activities which do not meet the conditions for the exemptions
described in Sec. 725.232, 725.234, or 725.238 may report under this
subpart.
(b) A person may report under this subpart for the following
research and development activities:
(1) A person who intends to manufacture or import for commercial
purposes a new microorganism.
(2) A person who intends to manufacture, import, or process for
commercial purposes a microorganism identified in subpart M of this
part as a significant new use. Additional reporting requirements for
significant new uses are described in subpart L of this part.
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) Meets the requirements of Sec. 725.234(a) and (c).
(b) Is receiving research funds from another Federal agency which
controls the research in accordance with applicable portions of the NIH
``Guidelines for Research Involving Recombinant DNA Molecules.'' This
control may be exercised through direct regulatory authority or through
requiring compliance with the NIH Guidelines as a condition of
receiving funds.
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 TQI'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 the containment and/or inactivation controls,
including contingency plans for emergency clean-up or test termination,
that will be used during the test. These records, which must be
maintained at the location where the research and development activity
is being conducted, shall be submitted to the Agency at the Agency's
written request and within the time frame specified in the Agency's
request.
(4) Subsequent to Agency 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 Agency order. Failure to comply with the Agency's
order shall result in automatic loss of eligibility for an exemption
under this section.
(e) The manufacturer, importer, or processor notifies all persons
in its employ or to whom it directly distributes the microorganism, who
are engaged in experimentation, research, or analysis on the
microorganism, including the manufacture, processing, use, transport,
storage, and disposal of the microorganism associated with research and
development activities, of any risk to health, identified under
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. (1) To determine whether notification
under Sec. 725.234(e) is required, 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 section 4, 5, or 6 of the Act that applies to the
microorganism and of which the manufacturer, importer, or processor has
knowledge.
(2) When the research and development activity is conducted solely
inside a laboratory and exposure to the microorganism is controlled
through the implementation of prudent practices for handling
microorganisms of unknown human health or environmental effects and any
distribution, except for purposes of disposal, is to other such
laboratories for further research and development activity, the
information specified in paragraph (a)(1) of this section need not be
reviewed and evaluated. (For purposes of this paragraph (a)(2), a
laboratory is defined as a contained research facility, where
relatively small quantities of microorganisms are used on a non-
production basis, and where activities involve the use of containers
for reactions, transfers, and other handling of microorganisms designed
to be easily manipulated by a single individual.)
(b) Notification to employees. (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)(1) 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.
(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) No applicability to general commercial use. 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, except where the microorganism is processed,
distributed in commerce, or used only as an impurity or as part of an
article.
(d) Waste disposal. 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.
(e) Impurities and articles. Quantities of research and development
microorganisms existing solely as impurities in a product or
incorporated into an article, in accordance with paragraph (c) of this
section, are not subject to the requirements of Sec. 725.234 and
paragraphs (a) and (b) of this section, once research and development
activities have been completed.
(f) Pesticide uses. 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 the
person's exclusive intention is to perform research and development
activities solely for the purpose of determining whether the
microorganism can be used as a pesticide.
(g) Recordkeeping. A person who manufactures, imports, or processes
a microorganism under this section must retain the following records:
(1) 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.
(2) Copies or citations to information reviewed and evaluated under
paragraph (a)(1) of this section to determine the need to make any
notification of risk.
(3) Documentation of prudent laboratory practices used instead of
notification and evaluation under paragraph (a)(2) of this section.
(4) Documentation of the nature and method of notification under
paragraph (b)(1) of this section, including copies of any labels or
written notices used.
(5) 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 phone 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) Notification of the appropriate Federal and state authorities
of the planned test.
(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.
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 antibiotic resistance, the structural gene may originate
from any source.
(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 5 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 antibiotic resistance, the structural gene may originate
from any source.
(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 5 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 this subpart.
General requirements for all submissions under this part are
contained in Sec. 725.25. In addition, the following requirements apply
to applications 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 prior to initiating 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
Sec. Sec. 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 described under Sec. 725.205 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 and remains liable
for compliance with all terms, 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.
(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 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 cells released (including viability per volume if
applicable) and the method(s) of application or release.
(iii) Characteristics of the test site(s), including location,
geographical, physical, chemical, and biological features, proximity to
human habitation or activity, and description of site characteristics
that would influence dispersal or confinement.
(iv) Target organisms (if the microorganism(s) to be tested has an
intended target), including identification of each target organism and
anticipated mechanism and result of interaction.
(v) Planned start date and duration of each activity.
(vi) Evidence that State authorities have been notified.
(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, 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 human 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 Sec. Sec. 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 human 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 conditions in its approval of the TERA that
would be stated in a TERA agreement under paragraph (c) of this
section.
(4) If EPA concludes that the proposed research and development
activity may present an unreasonable risk of injury to human health or
the environment, EPA will deny the TERA and will provide reasons for
the denial in writing.
(c) TERA agreement. (1) The TERA agreement is legally binding on
the TERA submitter and the Agency. The TERA submitter agrees to be
bound by the requirements set out in the agreement and also certifies
that all data submitted to the Agency is true and correct.
(2) If EPA approves a TERA, the submitter must conduct the research
and development activity only as described in the TERA agreement and in
accordance with any conditions set forth by EPA in its approval of the
TERA agreement.
(3) Any person who fails to comply with any requirement or
condition of the TERA agreement shall be in violation of sections 5 and
15 of TSCA and so subject to civil and criminal penalties under section
16 of TSCA.
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 the Agency's determination that the
activity does not present an unreasonable risk of injury to human
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 it will continue to approve the TERA, it
will notify the submitter in writing. In continuing to approve a TERA,
EPA may prescribe additional conditions which must be followed by the
submitter. In this case, EPA may reserve the right to review the test
data and revoke the TERA approval after some time period.
(ii) If EPA concludes that it can no longer approve the TERA, it
will notify the submitter in writing 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 receives information which indicates that the
proposed research and development activity will present an unreasonable
risk of injury to human health or the environment, EPA will notify the
submitter in writing and state its reasons.
(2) The submitter must provide additional safeguards or terminate
the research and development activity in accordance with directions
provided by EPA in the notice.
(3) 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 under paragraph
(a)(3) of this section.
(5) The submitter may resume the activity only upon written notice
from EPA that EPA has approved resumption of the activity. In approving
resumption of an activity, EPA may prescribe additional conditions
which must be followed by the submitter.
(c) Modifications. If, after approval of a TERA under this subpart,
the submitter concludes that it is necessary to alter the conduct of
the research and development activity in a manner which would result in
the activity being different from that described in the TERA agreement
and any 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 report 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 report 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 as a significant new use.
Sec. 725.350 Procedural requirements for this subpart.
General requirements for all submissions under this part are
contained in Sec. 725.25. In addition, the following requirements apply
to applications submitted under this subpart:
(a) Prenotice consultation. EPA strongly suggests that for a TME,
the submitter contact the Agency for a prenotice consultation regarding
eligibility for a TME.
(b) When to submit a TME. Each manufacturer or importer who is
eligible to submit a TME under this subpart must submit the TME at
least 45 calendar days before commencing 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 submitter 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 Sec. Sec. 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--Exemption for Microorganisms in General Commercial Use
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 general
commercial use.
(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 exemption request. The limited reporting requirements for the
Tier II exemption, including data requirements, are described in
Sec. Sec. 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 part:
(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.
(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. The introduced genetic material must
not contain any part of the nucleotide sequences that encode the toxins
described in this paragraph (d). Although these toxins are listed
according to the source organism, it is use of the nucleotide sequences
that encode the toxins that are 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.
Similar or identical sequences may be isolated from organisms other
than those listed below. Comparable toxin sequences, regardless of the
organism from which they are derived, must not be included in the
introduced genetic material. Toxin synonyms are included in
parentheses.
(1) Sequences for protein synthesis inhibitor.
Sequence Source Toxin Name
Corynebacterium diphtheriae & C. Diphtheria toxin
ulcerans
Pseudomonas aeruginosa Exotoxin A
Shigella dysenteriae Shigella toxin (Shiga toxin,
Shigella dysenteriae type I toxin,
Vero cell toxin)
Abrus precatorius, seeds Abrin
Ricinus communis, seeds Ricin
(2) 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
(3) 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
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)
(4) 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 (LT); Heat-
Enterobacteriaceae spp. stable enterotoxins (STa, ST1
subtypes ST1a ST1b; also STb,
STII)
Legionella pneumophila Cytolysin
Vibrio cholerae & Vibrio mimicus Cholera toxin (choleragen)
(5) 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), Ovis
Corynebacterium spp. toxin (sphingomyelinase D)
Staphylococcus aureus Beta-lysin (beta toxin)
(6) 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, Vero
Enterobacteriaceae spp. 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, cytotoxin)
aeruginosa
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.
All of the following criteria for the physical containment and
control technologies of the facility are required for a Tier I
exemption and serve as guidance for a Tier II exemption:
(a) The structure is designed and operated to contain the
microorganisms.
(b) Limit entry only to those persons whose presence is critical to
the reliability or safety of the activity.
(c) Provide written, published, and implemented procedures for the
safety of personnel and control of hygiene.
(d) Include 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 microbial concentrations by at least 6 logs in
liquid and solid wastes.
(e) Provide and document effectiveness of features to reduce
microbial concentration by at least 2 logs in aerosols and exhaust
gases released from the structure.
(f) Include and document systems for controlling dissemination of
the microorganisms through other routes.
(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 general commercial use is not subject to review under
this part if all of the following conditions are met:
(1) The recipient microorganism is listed 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 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 30 days before commencing
initial manufacture or import.
(5) The manufacturer or importer complies with the recordkeeping
requirements of Sec. 725.65 and maintains records 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 exemption under this
subpart, a 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) Certification of the following:
(i) The recipient microorganism is one of those listed in
Sec. 725.420
(ii) Compliance with the introduced genetic material criteria
described in Sec. 725.421.
(iii) Compliance with the containment requirements described in
Sec. 725.422, including the provision in paragraph (a)(3) of this
section.
(4) The site of waste disposal and the type of permits for
disposal, the permit numbers and the institutions issuing the permits.
(5) The certification statement required in Sec. 725.25(b).
Sec. 725.426 Liability of the manufacturer or importer who uses 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
Sec. Sec. 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 general
commercial use 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 and meets any
requirements specified in Sec. 725.420.
(b) The introduced genetic material meets the criteria under
Sec. 725.421.
(c) 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 expedited review.
(b) When to submit the Tier II exemption request. Each manufacturer
or importer who is eligible to submit a Tier II exemption request under
this subpart must submit the request at least 45 calendar days before
commencing 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 Sec. Sec. 725.428 and 725.455, as well as information
sufficient to enable EPA to evaluate the effects of all activities
described in the request.
(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 applicant must indicate clearly that the submission is an 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.
Sec. 725.470 EPA review of the Tier II exemption request.
General procedures for review of all submissions under this part
are contained in Sec. Sec. 725.28 through 725.60. In addition, the
following procedures apply to EPA review of 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 use
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 Administrator, or a
designee, decides that there is insufficient information to determine
that the conditions of use 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 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 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.
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 Sec. Sec. 725.910 and 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 Sec. Sec. 725.980 and 725.984.
Sec. 725.910 Persons excluded from reporting on 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.
(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.
(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.
(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 intends to manufacture, import, or process a
microorganism described in subpart M of this part and intends to
distribute 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 Monitoring (EN-342),
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
(2) If EPA notifies the manufacturer, importer, or processor that
the recipient is engaging in a significant new use after providing the
statement of assurance described in paragraph (d)(1)(ii) of this
section and without submitting a MCAN under this part, the
manufacturer, importer, or processor shall immediately cease
distribution to that recipient until the manufacturer, importer, or
processor or the recipient has submitted a MCAN under this part and the
MCAN review period has ended.
(3) If, after receiving a statement of assurance from a recipient
under paragraph (d)(1)(ii) of this section, a manufacturer, importer,
or processor has knowledge that the recipient is engaging in a
significant new use without submitting a MCAN under this part, the
manufacturer, importer, or processor must immediately cease
distributing the microorganism to that recipient and notify EPA
enforcement authorities at the address identified in paragraph
(c)(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. Sec. 725.100(c) and 725.910 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 Sec. Sec. 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, Sec. Sec. 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.
(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 40 CFR part 707.
(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 Sec. Sec. 12.118 through 12.127 and 12.28. The EPA
policy in support of the import certification requirements appears at
40 CFR part 707.
Sec. 725.950 Additional recordkeeping requirements for reporting of
significant new uses.
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,
the Agency 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 the Agency.
(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.
(5) The specifications of the alternative worker exposure control
measures or environmental release control measures.
(6) An analysis justifying 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 Sec. Sec. 725.155 and
725.160 of this part unless such data and information have already been
submitted to EPA's Office of Pollution Prevention and Toxics.
(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 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 M 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 the direct 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 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.
(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)(5)(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 of this part.
(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) For a microorganism added to subpart M of this part under
Sec. 725.980, 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 human
health or the environment required under section 5(e)(1)(A) of the Act.
(5) For a microorganism added to subpart M of this part under
Sec. 725.980, 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--[Reserved]
[FR Doc. 94-21359 Filed 8-31-94; 8:45 am]
BILLING CODE 6560-50-F