17910 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

ENVIRONMENTAL PROTECTION

AGENCY

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

725

[OPPTS–00049C; FRL–5577–2]

RIN 2070-AB61

Microbial Products of Biotechnology;

Final Regulation Under the Toxic

Substances Control Act

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Final rule.

SUMMARY: EPA is promulgating this final

rule under section 5 of the Toxic

Substances Control Act (TSCA), 15

U.S.C 2604, to establish notification

procedures for review of certain new

microorganisms before they are

introduced into commerce. ‘‘New’’

microorganisms are those formed by

deliberate combinations of genetic

material from organisms classified in

different taxonomic genera. This review

process is designed to prevent

unreasonable risk of injury to human

health and the environment without

imposing unnecessary regulatory

burdens on the biotechnology industry.

This final rule describes notification

procedures and the microorganisms that

would be exempt from notification.

DATES: This rule will become effective

June 10, 1997. In accordance with 40

CFR 23.5, this rule shall be promulgated

for purposes of judicial review at 1 p.m.

eastern daylight savings time on April

27, 1997.

FOR FURTHER INFORMATION CONTACT: For

general information including copies of

this document and related materials:

Susan Hazen, Director, Environmental

Assistance Division (7408), Office of

Pollution Prevention and Toxics,

Environmental Protection Agency, 401

M St., SW., Washington, DC 20460,

Telephone: (202-554-1404), TDD: (202-

554-0551), e-mail address: TSCAHotline@epamail.epa.gov.

For technical information regarding

this document: David Giamporcaro,

Office of Pollution Prevention and

Toxics (7405), Environmental Protection

Agency, 401 M St., SW., Washington,

DC 20460. Telephone: (202-260-6362).

SUPPLEMENTARY INFORMATION:

Electronic Availability: Electronic

copies of this document and various

support documents are available from

the EPA home page at the

Environmental Sub-Set entry for this

document under ‘‘Regulations’’ (http://

www.epa.gov/fedrgstr/). The final rule

may also be accessed at the Office of

Pollution Prevention and Toxics

Biotechnology home page at http://

www.epa.gov/opptintr/biotech/. FaxOn-Demand: Using a faxphone call 202–

401–0527 and select item 3100 for an

index of available material and

corresponding item numbers related to

this document.

This rule establishes procedures for

the premanufacture review of certain

new microbial products of

biotechnology that are comparable to

those for traditional chemical

substances but are tailored to address

the specific characteristics of these

microorganisms. EPA published its final

TSCA section 5 premanufacture

notification (PMN) rule (40 CFR part

720) on May 13, 1983 (48 FR 21722) and

subsequently amended certain parts of

the rule on September 13, 1983 (48 FR

41132), April 22, 1986 (51 FR 15096),

and March 29, 1995 (60 FR 16298)

(FRL–4921–8). In 1984, EPA discussed

how the PMN rule could be applied to

microorganisms in ‘‘Proposed Policy

Regarding Certain Microbial Products’’

which was published as part of the

Federal ‘‘Proposal for a Coordinated

Framework for Regulation of

Biotechnology; Notice’’ (‘‘1984 Proposed

Policy Statement’’) which was

published by the Office of Science and

Technology Policy (OSTP) on December

31, 1984 (49 FR 50856). In 1986, EPA

stated how the PMN rule would be

applied to microorganisms in the

‘‘Statement of Policy: Microbial

Products Subject to the Federal

Insecticide, Fungicide, and Rodenticide

Act and Toxic Substances Control Act’’

(‘‘1986 Policy Statement’’), which was

published as part of the Federal

‘‘Coordinated Framework for Regulation

of Biotechnology; Announcement of

Policy and Notice for Public Comment’’

which was published by OSTP on June

26, 1986 (51 FR 23302). On September

1, 1994, EPA published the proposed

rule, ‘‘Microbial Products of

Biotechnology; Proposed Regulation

Under the Toxic Substances Control

Act,’’ which would, when finalized,

fully implement its program for

microorganisms under TSCA section 5

(59 FR 45526) (FRL–4778–4). While

general background information is

presented here, readers should also

consult the preambles of those

documents for further information on

the development of the biotechnology

program under TSCA section 5.

Regulated Entities. Potentially regulated

entities are persons conducting

commercial research and development

activities or persons manufacturing,

importing, or processing for commercial

purposes intergeneric microorganisms

used for a TSCA purpose. Regulated

categories and entities include:

Category Examples of Regulated Entities

Biotechnology research and development activities involving commercial fundsPersons conducting commercial research using intergeneric microorganisms for biofertilizers; biosensors; biotechnology reagents; commodity or specialty chemical production; energy applications; waste treatment or pollutant degradation; and other TSCA subject uses.

Commercial biotechnology products Persons manufacturing, importing or processing products for commercial purposes intergeneric microorganisms for biofertilizers; biosensors; biotechnology reagents; commodity or specialty chemical production; energy applications; waste treatment or pollutant degradation; and other TSCA subject uses.

This table is not intended to be

exhaustive, but rather provides a guide

for readers regarding entities likely to be

regulated by this action. This table lists

the types of entities that EPA is now

aware could potentially be regulated by

this action. Other types of entities not

listed in the table could also be

regulated. To determine whether your

intergeneric microorganism is regulated

by this action, you should carefully

examine the list of substances excluded

by TSCA section (3)(2)(B), and the

requirements for ‘‘persons who must

report’’ in § 725.205 of the regulatory

text for research and development

activities using intergeneric

microorganisms and § 725.105 of the
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17911

regulatory text for manufacturing,

importing, and processing intergeneric

microorganisms. If you have questions

regarding the applicability of this action

to a particular entity, consult the person

listed in the preceding FOR FURTHER

INFORMATION CONTACT UNIT.

I. Background

A. Statutory Authority

TSCA section 5(a)(1) requires that

persons notify EPA at least 90 days

before they manufacture or import for

commercial purposes a ‘‘new’’ chemical

substance or manufacture, import, or

process a chemical substance for a

‘‘significant new use.’’ TSCA defines

‘‘chemical substance’’ broadly and in

terms which cover microorganisms as

well as traditional chemicals. Therefore,

for the purposes of TSCA, a ‘‘new

microorganism,’’ like a ‘‘new chemical

substance,’’ is one that is not listed on

the TSCA Chemical Substances

Inventory compiled under TSCA section

8(b). TSCA section 5(h)(3) exempts the

manufacture or importation of small

quantities of chemical substances

produced solely for research and

development (R&D) from the section 5

notification requirements if the

manufacturer or importer notifies

persons engaged in R&D of any health

risks that the company or EPA has

reason to believe may be associated with

the chemical substance. TSCA section

5(h)(3) authorizes EPA to define by rule

what constitutes small quantities and to

prescribe the form and manner of risk

notification. TSCA section 5(h)(4)

authorizes EPA, upon application and

by rule, to exempt the manufacturer or

importer of any new chemical substance

from part or all of the provisions of

section 5, if EPA determines that the

manufacture, processing, distribution in

commerce, use, or disposal of the new

chemical substance will not present an

unreasonable risk of injury to human

health or the environment.

B. History

This rule implements EPA’s program

for oversight of microorganisms, in

accordance with the 1986 Policy

Statement. Since its publication, EPA

has been operating its biotechnology

program under the 1986 Policy

Statement. Prior to the 1986 Policy

Statement, EPA issued the 1984

Proposed Policy Statement. Subsequent

to the 1986 Policy Statement, EPA

issued a notice, entitled ‘‘Biotechnology;

Request for Comment on Regulatory

Approach’’ on February 15, 1989 (54 FR

7027), in order to solicit comments on

the direction of EPA’s biotechnology

program under TSCA. Comments on the

1984 and 1986 documents and the

February 15, 1989 Federal Register

notice are addressed, as appropriate, in

this preamble.

On September 7, 1990, EPA convened

a subcommittee of its Biotechnology

Science Advisory Committee

(Subcommittee on Implementation of

Scope) to comment on topics associated

with the proposed rule. EPA again

convened a subcommittee, the

Subcommittee on the Proposed

Biotechnology Rule under TSCA, which

met on July 22, 1991. Advice from both

of these subcommittees was

incorporated as appropriate in the

preamble to the proposed rules, and

summaries of subcommittee

deliberations were placed in the docket

for this rulemaking. On September 1,

1994, EPA published the proposed rules

‘‘Microbial Products of Biotechnology;

Proposed Regulation Under the Toxic

Substances Control Act’’ (59 FR 45526).

The final rule announced today is

intended to describe implementation of

EPA’s program for regulation of

microorganisms under TSCA.

II. Summary of Proposed Rule

EPA proposed to establish a new part

725 of Title 40 of the Code of Federal

Regulations (CFR). EPA believed that

consolidating all requirements and

procedures applicable to new

microorganisms into one part of the CFR

was appropriate and justified because of

the specific characteristics of

microorganisms. The consolidation was

expected to benefit the public by

providing greater focus and enhanced

clarity. Part 725 is devoted exclusively

to the review of microorganisms under

section 5 of TSCA and is divided into

eight subparts. Subparts A, B, and C

consolidated provisions primarily

adapted from parts 720 and 721.

Subpart A, which includes definitions

that are applicable throughout part 725,

described general provisions and

applicability. Subpart B described

administrative procedures that are

applicable to all submissions under part

725. Subpart C described confidentiality

provisions that are applicable to all

submissions under part 725.

Subpart D, which combined the

general PMN and significant new use

notice (SNUN) requirements adapted

from parts 720 and 721, described the

reporting requirements and review

process pertaining to microbial

commercial activity notices (MCANs).

Subparts E, F, and G described the

reporting requirements and review

processes for applications for

exemptions from full MCAN reporting.

Subpart E, which was almost entirely

new, described a new reporting process

using the TSCA experimental release

application (TERA) which was

developed for reporting research and

development (R&D) activities involving

release to the environment. Subpart E

also described who would be eligible to

submit a TERA or receive a TERA list

exemption, and the criteria that must be

met to receive an exemption from EPA

review for certain types of R&D

activities. Subpart F, which was an

adaptation of § 720.38, described the

requirements for a test marketing

exemption for microorganisms. Subpart

G, which was entirely new, described

the criteria that must be met in order to

qualify for Tier I or Tier II exemptions

for certain microorganisms in general

commercial use. Subpart L, which was

adapted from part 721, described

additional procedures for reporting

significant new uses of microorganisms.

Although significant new use rules were

not being proposed, it was intended that

subpart M would list microorganisms

and specific significant new uses when

they were promulgated.

In addition, EPA proposed to amend

existing regulations regarding the

collection of fees from submitters of

notices under section 5 of TSCA (40

CFR part 700), to reflect the fee structure

for the notices and applications that

have been developed by these proposed

rules. Additional amendments to parts

720, 721, and 723 were proposed to

consolidate TSCA section 5 review of

microorganisms into part 725.

III. Summary of Final Rule

This final rule establishes all

reporting requirements under section 5

of TSCA for manufacturers and

processors of microorganisms subject to

TSCA jurisdiction, that are

manufactured for commercial purposes,

including research and development for

commercial purposes. The rule

establishes a number of mechanisms for

reporting to EPA, including a number of

specific exemptions. Most of the

exemptions create an alternative

mechanism for reporting to EPA that

reduces the amount of information to be

reported. Certain of the research and

development exemptions establish the

conditions under which no reporting

would be required.

Manufacturers are required to report

certain information to EPA 90 days

before commencing the manufacture of

intergeneric microorganisms that are not

listed on the TSCA Inventory. The rule

establishes the mechanism for reporting

this information. The rule also defines

‘‘small quantities for research and

development’’ for microorganisms; the

effect of which is to require section 5
17912 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

reporting for certain research and

development activities.

Any manufacturer, importer, or

processor of a living microorganism,

who is required to report under section

5 of TSCA must file a Microbial

Commercial Activity Notice (MCAN)

with EPA, unless the activity is eligible

for one of the specific exemptions. The

general procedures for filing MCANs are

described in subpart D of part 725 of the

regulatory text.

TSCA section 5 only applies to

microorganisms that are manufactured,

imported, or processed for commercial

purposes. EPA has defined manufacture

or process for commercial purposes as

‘‘manufacture or process for purposes of

obtaining an immediate or eventual

commercial advantage.’’ Whether an

activity has an immediate or eventual

commercial advantage is determined by

indicia of commercial intent. Research

and development activities are for

commercial purposes, and thus subject

to reporting, if tests are directly funded,

in whole or in part by a commercial

entity, when the researcher considers

there to be an immediate or eventual

commercial advantage. In addition, all

post R&D activities are considered

manufacture or processing for a

commercial purpose.

EPA has established two exemptions

for new microorganisms, after the R&D

development stage, which are being

manufactured for introduction into

commerce. In the Tier I exemption, if

three criteria are met, manufacturers are

only required to notify EPA that they are

manufacturing a new microorganism

that qualifies for this exemption 10 days

before commencing manufacture, and to

keep certain records. A manufacturer is

not required to wait for EPA approval

before commencing manufacture. To

qualify for the Tier I exemption, a

manufacturer must use one of the listed

recipient organisms and must

implement specific physical

containment and control technologies.

In addition, the DNA introduced into

the recipient microorganism must be

well-characterized, limited in size,

poorly mobilizable, and free of certain

sequences.

A manufacturer, who otherwise meets

the conditions of the Tier I exemption,

may modify the specified containment

restrictions, but must submit a Tier II

exemption notice. The Tier II exemption

requires manufacturers to submit an

abbreviated notice describing the

modified containment, and provides for

a 45–day period, during which EPA

would review the proposed

containment. The manufacturer may not

proceed under this exemption until EPA

approves the exemption.

Rather than submitting a MCAN

during research and development,

manufacturers may qualify for one of

several exemptions, or may choose to

submit to EPA a TSCA Experimental

Release Application.

If a manufacturer is conducting

research and development activities

solely within a contained structure, the

research may qualify for one of two

exemptions. For contained research

conducted by researchers who are

required to comply with the NIH

guidelines, EPA has established a

complete exemption from EPA review

and reporting and recordkeeping

requirements. For all other

manufacturers conducting contained

research and development activities

EPA has established a more limited

exemption. The exemption specifies

factors which the technically qualified

individual must consider in selecting

the appropriate containment. The

manufacturer is required to keep records

to document compliance with the

containment requirements, but is

exempt from all other TSCA section 5

reporting requirements. See Unit V.C.5.

of this preamble.

For researchers conducting smallscale field tests with Bradyrhizobium

japonicum and Rhizobium meliloti, the

final rule creates an exemption from

EPA review, providing certain

conditions are met. The field testing

must occur on no more than 10

terrestrial acres; the introduced genetic

material must comply with certain

restrictions, and appropriate

containment measures must be selected

to limit dissemination.

If a manufacturer does not meet the

requirements for one of the exemptions

discussed above, he or she may submit

a TERA. The TERA is essentially an

abbreviated MCAN submission for

individual tests. EPA’s review period is

reduced to 60 days, although EPA may

extend the period for good cause. EPA

must approve the test before the

researcher may proceed, even if the 60-

day period expires. EPA’s approval is

limited to the conditions outlined in the

TERA notice or approval.

In addition, a manufacturer may

submit a MCAN for any R&D activity.

However, EPA expects that most

researchers will instead choose to

submit a TERA. In addition to the longer

review period, EPA expects that,

because of the limited information at the

R&D stage, the Agency would likely

issue a section 5(e) order to impose

conditions to address the uncertainties,

which would need to be modified each

time the manufacturer wanted to vary

the terms of the order.

IV. Summary of Major Changes in Final

Rule

The final rule adopts the provisions of

the proposed rule with few revisions.

EPA is adding to 40 CFR a new part 725,

which applies TSCA section 5

requirements specifically to

microorganisms. Subpart A of part 725

contains general provisions and

applicability. The final rule retains from

the proposal the definition of ‘‘new

microorganisms’’ that are subject to

TSCA section 5 reporting. ‘‘New

microorganisms’’ are intergeneric

microorganisms that are not already

listed on the TSCA Inventory.

‘‘Intergeneric microorganism’’ is defined

at § 725.3. EPA has made some minor

revisions to definitions in § 725.3

related to scope of oversight.

Subpart B of part 725 contains

administrative procedures that have

been adapted with little change from

provisions in 40 CFR parts 720 and 721.

The provisions in the final rule have

been adopted with minor changes from

those proposed in 1994.

Subpart C of part 725 contains

requirements for claiming confidential

business information (CBI). These

requirements, which were adapted from

provisions in part 720, have not been

changed from the proposal, with the

exception of the requirement relating to

CBI claims in the TERA and other minor

changes. Section 725.94(a)(2) has been

modified to eliminate the proposed

requirement for upfront substantiation

of CBI claims in the TERA submission.

Subpart D establishes the reporting

program for new microorganisms

manufactured or imported for

distribution into commerce and requires

submission of a MCAN 90 days prior to

initiating manufacture or import of the

new microorganism. This subpart

codifies the requirements for

information to be included in the

MCAN at §§ 725.155 and 725.160 and is

promulgated with minor changes from

the proposal.

Subpart E establishes the exemptions

from full MCAN reporting for R&D

activities. At § 725.205(b), EPA defines

‘‘commercial purposes’’ for R&D

activities to include all R&D directly

funded in whole or in part by a

commercial entity, and all R&D

activities, regardless of funding source,

for which the researcher intends to

pursue immediate or eventual

commercial advantage.

Subpart E establishes, at § 725.232, a

complete exemption from TSCA section

5 obligations for certain R&D activities

conducted in contained structures and

subject to regulation by another Federal

agency. EPA establishes another
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17913

exemption from reporting requirements

for R&D activities in contained

structures which meet the requirements

of §§ 725.234 and 725.235.

Subpart E also establishes at

§§ 725.238 and 725.239 the TERA

exemption process for R&D activities,

primarily those involving intentional

environmental release. EPA has revised

requirements in § 725.239 to limit the

antibiotic resistance markers that may

be used in the microorganisms eligible

for the TERA exemption.

Subpart E codifies the requirements

for information that must be included in

the TERA at §§ 725.255 and 725.260,

and is promulgated with minor changes

from the proposal. EPA has revised the

requirements at §§ 725.238(b)(3)(ii) and

725.255(e)(1)(vi) with regard to

notification of State and/or local

authorities.

Subpart F contains the requirements

for exemptions for test marketing

activities. These requirements have been

adapted, with little change, from

provisions in part 720 and have only

minor changes from the 1994 proposed

rule.

Subpart G establishes an exemption

from MCAN reporting for certain

microorganisms and places

requirements on the recipient

microorganism, the introduced genetic

material, and the physical containment.

Some changes have been made to

requirements for specific eligibility

criteria since the proposal. Section

725.421 contains the requirements for

the introduced genetic material. Minor

changes have been made to § 725.421(d)

to clarify the functional portions of

toxin-encoding sequences that cannot be

included in the introduced genetic

material. Section 725.422 contains the

requirements for physical containment.

Section 725.422(b) has been revised to

require controlled access to the

structure. Section 725.422(e) has been

modified to require submitters to

document the effectiveness of the

features used to minimize the microbial

concentrations in aerosols and exhaust

gases released from the structure.

Subpart L establishes procedures for

reporting significant new uses of

microorganisms. These requirements

have been adapted, with little change,

from provisions in part 721 and have

only minor changes since they were

proposed in 1994.

Subpart M is reserved for

requirements for significant new uses

for specific microorganisms; however,

none are being promulgated in this rule.

The regulatory text also amends

existing regulations regarding the

collection of fees from submitters of

notices under section 5 of TSCA (40

CFR part 700), to reflect the fee structure

for the notices and applications that

have been developed by this rule.

Additional amendments to parts 720,

721, and 723 consolidate TSCA section

5 review of microorganisms into part

725.

V. Discussion of Final Rule and

Response to Comments

In response to the proposed rule, EPA

received 40 letters from the public

during the comment period. Comments

were received from industry, academia,

professional and trade associations,

government agencies, public interest

groups, and individuals. While all

commenters raised issues about specific

aspects of the rule, several commenters

indicated that they generally supported

it. Some commenters had major

concerns about the rule and suggested

modifications that would have

significantly changed the nature of the

rule as it was proposed. EPA reviewed

and considered all comments received

on the proposed rule and prepared

detailed responses to the comments.

Copies of all comments received along

with EPA’s ‘‘Summary of Public

Comments and EPA’s Response’’ are

available in the public docket for this

rulemaking. A discussion of the final

rule, including a summary of significant

comments and EPA’s responses follows.

A. Coverage of Microorganisms under

TSCA

EPA continues to believe that the

TSCA section 3(2) definition of

‘‘chemical substance’’ gives EPA

authority to review microorganisms

under TSCA. EPA is retaining its

interpretation of ‘‘new’’ microorganisms

as stated in the 1986 statement policy

and the proposed rule. Under that

interpretation, microorganisms resulting

from deliberate combinations of genetic

material from organisms classified in

different genera constitute ‘‘new’’

microorganisms subject to section 5

reporting requirements. EPA terms such

microorganisms intergeneric. For the

purposes of this rule, EPA will treat

mobile genetic elements, those elements

of genetic material that have the ability

to move genetic material within and

between organisms, as follows: The term

‘‘intergeneric microorganism’’ includes

a microorganism which contains a

mobile genetic element which was

originally isolated from a

microorganism in a genus different from

the recipient microorganism. Excluded

from the definition of ‘‘intergeneric

microorganism’’ are microorganisms

which contain introduced genetic

material consisting solely of wellcharacterized, non-coding regulatory

regions from organisms in another

genus. These terms are defined at

§ 725.3.

1. Intergeneric scope. EPA has

decided to define ‘‘new

microorganisms’’ as those

microorganisms resulting from the

deliberate combination of genetic

material originally isolated from

organisms classified in different genera

because of the degree of human

intervention involved, the significant

likelihood of creating new combinations

of traits, and the greater uncertainty

regarding the effects of such

microorganisms on human health and

the environment. This approach, based

on a taxonomic standard, both identifies

a group of microorganisms whose

behavior in the environment poses

significant uncertainty, which therefore

warrant regulatory review under TSCA

section 5, and provides a way of

defining ‘‘new’’ microorganisms under

TSCA section 5.

TSCA section 5 requires all

manufacturers of new chemical

substances to submit information to

EPA 90 days before commencing

commercial manufacture, to permit EPA

to examine whether they may present an

unreasonable risk of injury to health and

the environment. As discussed at greater

length in Unit II. of the Response to

Comments Document, the rationale for

the requirement was to have EPA

attempt to resolve the uncertainties

surrounding the class of new chemical

substances--specifically, whether they

were likely to cause unreasonable risks

before they were introduced into the

environment.

When considering the various

approaches that could be used to define

a ‘‘new’’ microorganism for TSCA

purposes, one important factor EPA took

into account was the regulatory

precedents established in compiling the

inventory of existing chemical

substances under section 8(b) of TSCA.

Any chemical substance not on the

Inventory is ‘‘new’’ under section 5(a) of

TSCA and is therefore subject to

premanufacture reporting. Naturally

occurring substances and substances

derived from nature with limited human

intervention are considered to be

automatically included on the

Inventory, and thus are not ‘‘new.’’ EPA

concluded that microorganisms found

in nature could also be considered not

new because they occur naturally,

without human intervention, and

therefore, ‘‘naturally occurring

microorganisms’’ are automatically

listed on the TSCA Inventory, and are

not subject to this rule.

Second, EPA considered that modern

biotechnology techniques permit genetic
17914 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

material to be intentionally moved

between and combined in disparate

organisms. On occasion the genetic

material combined would not be genetic

material expressing traits possessed by

both the donors of the genetic material

and the recipients. In other words, the

genetic material encoding these traits

would not be commonly shared between

the donor and recipient organisms.

Microorganisms formed from genetic

material not commonly shared by

donors and recipients would have a

significantly higher probability of

exhibiting new traits or new

combinations of traits compared to

naturally occurring microorganisms.

Some of the microorganisms developed

through modern biotechnology may

exhibit new or altered traits affecting,

for example, their survivability, host

range, substrate utilization,

competitiveness with other organisms,

or protein or polysaccharide production.

The behavior of organisms expressing a

new trait or new combinations of traits

is thus less predictable and their

probable behavior less certain. EPA

chose to focus particular regulatory

attention on microorganisms that have a

higher potential for exhibiting a new

trait or combinations of traits.

EPA decided that a standard based on

the taxonomic taxon of genus defined a

class of sufficiently high probability of

exhibiting a new trait or new

combinations of traits to warrant review.

Taxonomy is a system of orderly

classification of organisms according to

their presumed natural relationships.

Since the organisms contributing

genetic material to intergeneric

microorganisms are, in general, more

distantly related than the

microorganisms contributing genetic

material to intrageneric microorganisms

(and thus less likely to have traits in

common), intergeneric microorganisms

have a higher probability of exhibiting

a new trait or new combinations of traits

and their behavior is therefore

significantly less predictable than

intrageneric microorganisms.

A scope based on a taxonomic

standard such as intergeneric has

certain advantages. A taxonomy based

scope relates directly to the potential of

the resulting new microorganism to

display a new trait or new combinations

of traits, since organisms that share a

close evolutionary ancestry are more

likely to have traits in common than

those that are more distantly related. In

addition, the taxonomy standard is

independent of the technology used to

create the microorganism. A number of

techniques may be used to produce

intergeneric microorganisms. Any

intergeneric microorganisms created by

techniques developed in the future

would also be subject to this final rule.

Taxonomy reflects current scientific

observations about phenotypic, and to a

certain extent, genotypic, differences

between organisms. Although subject to

periodic revision within the scientific

community, taxonomy is a common

language used by scientists. Basing the

standard for interpreting ‘‘new’’ for

microorganisms on an existing system

for categorizing organisms obviates the

need to create another system for

determining if a microorganism is

subject to reporting under TSCA section

5. Taxonomy is understood by the

regulated community and its use

imposes little, if any, additional burden

to determine whether a microorganism

is new.

For circumscribing what is new for

TSCA section 5, microbial taxonomy is

a relatively clear and objective criterion

for scope of oversight and thus provides

clarity for both the regulated community

and the Agency for enforcement

purposes. Taxonomic designations

provide a widely available standard and

point of reference. It is reasonable to

expect a manufacturer to use the

taxonomic literature and/or taxonomists

to determine currently accepted names

of organisms they wish to utilize. Once

a manufacturer knows the genus of a

microorganism, he or she can readily

determine whether a microorganism is

intergeneric and thus whether it is

‘‘new’’ within the section 5 context.

EPA recognizes that taxonomy,

particularly microbial taxonomy, is

subject to change and that new

information concerning organisms’

properties and relationships could alter

taxonomic designations. In recent years,

new tools have become available to

microbial taxonomists which have

allowed them to clarify phylogenic

relationships among microorganisms.

Some microbial genera are highly

defined and consist of closely related

members which are likely to share

common information in their genetic

material. However, other microbial

genera may consist of members more

closely related to microorganisms

classified in other genera than to each

other. While reorganizations could

result in changes in taxonomic

designations for some microorganisms

in the short term, it should result in

greater stability in the various taxa in

the long term. EPA anticipates that as

reclassifications occur in the scientific

community, the intergeneric standard

will become a better reflection of the

probability of new traits or new

combination of traits resulting from the

deliberate combining of genetic

material. However, even under current

taxonomic designations, gene exchange

is generally less likely to occur naturally

among members of different microbial

genera than among members of the same

genus, and this suggests a new trait or

new combinations of traits are more

likely to occur when genetic material

from microorganisms in different

taxonomic genera are combined.

Moreover, the probability of a new trait

or new combination of traits occurring

increases when the organisms

combining genetic material are more

distantly related; e.g., even among the

microorganisms, bacteria classified in

different genera are more likely to share

common traits than bacteria and fungi,

and bacteria classified in different

genera are more likely to share traits

than bacteria with plants and animals.

While taxonomic reorganizations could

affect the status, for TSCA purposes, of

some microorganisms formed by

combining genetic material from some

relatively closely related

microorganisms, the TSCA section 5

status of microorganisms formed by

combining genetic material of more

distantly related organisms is unlikely

to be affected. These considerations

suggest that while taxonomy may not be

a perfect standard, its use is likely to

capture for review those

microorganisms with a higher

probability of displaying new traits or

new combinations of traits. EPA

discusses in other parts of this preamble

and in the Response to Comments

document how it will accommodate

within its regulatory structure

reclassifications of microorganisms into

new or different taxa.

EPA believes that on whole, the

intergeneric definition generally

captures for review microorganisms

with a higher potential for displaying a

new trait or new combination of traits.

While this approach does have some

drawbacks, EPA believes that its

procedures are sufficiently flexible to

accommodate these drawbacks, and that

the advantages to using the intergeneric

definition outweigh the disadvantages.

EPA includes the phrase ‘‘originally

isolated’’ in the definition of

intergeneric to clarify that genetic

material belongs to the genus from

which it was originally isolated or

originally observed. For example, if a

sequence of genetic material was

originally introduced from

microorganism A into microorganism B,

subsequently reisolated from

microorganism B to be combined in

microorganism C, the manufacturer or

developer must consider the genera of

microorganisms A and C in determining

the status of the microorganism
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17915

resulting from the second combining

event described above.

2. Mobile genetic elements. In the

proposal (59 FR 45528), EPA also

discussed mobile genetic elements

(MGEs) and how it would apply its MGE

policy to the interpretation of ‘‘new’’

microorganisms for the purposes of

TSCA section 5. EPA has retained the

policy and incorporated it in its

definition of intergeneric

microorganism. MGEs, which are

elements of genetic material such as

plasmids and transposons, may in

nature move within or among organisms

and may carry with them and transfer

genetic material in addition to their

own. MGEs, which are used as vectors

for moving genetic material among

organisms, may move across taxonomic

boundaries and therefore are not a

constant part of the genome of one

particular taxonomic group or another.

After publication of the 1986 policy

statement describing EPA’s intergeneric

interpretation, several producers of

microorganisms inquired about the

status under TSCA of microorganisms

containing MGE material. Therefore, it

was necessary for EPA to develop an

approach for addressing MGEs under

the intergeneric interpretation. In

keeping with its intergeneric definition

which focused on the origin of the

introduced genetic material, EPA

decided that microorganisms would be

considered intergeneric if they

contained an MGE first identified in a

microorganism in a genus different from

the recipient microorganism genus.

Microorganisms would be considered

intrageneric, and not new, if the

literature indicates the MGE was first

identified in a microorganism in the

same genus as the recipient. EPA has

continued to use this policy regarding

MGEs to assist in determining whether

a microorganism is intergeneric.

The issue of whether the MGE may be

indigenous to the recipient genus is not

considered in EPA’s approach to

determining whether the final

microorganism is inter- or intrageneric.

The major consideration is the source of

the organism in which the MGE was

first identified. The source of the

organism in which the MGE was first

identified may be determined by a

search of relevant published scientific

literature or by reviewing available data

bases such as GENBANK. Such a

literature or data base reference is often

the first to name, and possibly describe,

the MGE. Subsequent references

postdating this first reference are

frequently not relevant for determining

the intergeneric status of the MGE, since

after isolation an MGE is often

transferred to a different taxon where it

can be more easily maintained and

studied. Although EPA recognizes that

MGEs may occur in more than one

genus in nature, EPA believes that for

the moment, use of the source of the

organism in which the MGE was first

identified for classifying MGEs provides

the most straightforward regulatory

approach under its intergeneric

definition. EPA will continue to use this

approach until it can reevaluate the

status of MGEs within an intergeneric

standard in a future rulemaking. EPA

has included a statement about MGEs in

its definition of intergeneric

microorganisms in this final rule.

3. Well-characterized, non-coding

regulatory regions. In the 1986 policy

statement and in the proposed rule, EPA

excluded from the definition of

intergeneric microorganisms, those

microorganisms that resulted from the

addition of intergeneric material that is

well-characterized and contains only

non-coding regulatory regions such as

operators, promoters, origins of

replication, terminators, and ribosomebinding regions. Where only regulatory

material is transferred, no distinctly

new combinations of traits are

introduced. Instead, quantitative

changes in existing traits in the

recipient microorganisms may occur.

EPA recognizes that insertion of wellcharacterized, noncoding regulatory

regions may result in expression of

previously cryptic regions. However, the

genetic material in cryptic regions is

present in the population and could be

expressed in some members of the

microbial population at any time

naturally. A microorganism expressing

such material as a consequence of

insertion of non-coding regulatory

regions would thus not be new under

TSCA. Therefore, EPA believes that

microorganisms formed through

intergeneric transfer of wellcharacterized, non-coding regulatory

regions should not be considered ‘‘new’’

microorganisms under TSCA section 5.

EPA emphasizes that this exclusion

applies only to intergeneric

microorganisms that have resulted

solely from the addition of wellcharacterized, non-coding, regulatory

regions. If the final microorganism

contains any regions from organisms of

other genera that do not meet this

restriction, such as coding regulatory

regions or any poorly characterized

regions, the microorganism is

considered new and is not eligible for

the exclusion.

In response to comments, EPA has

revised some of its definitions at § 725.3

relating to the intergeneric scope to

provide greater clarity for the regulated

community. The word ‘‘introduced’’ has

been added to the second sentence in

the definition of ‘‘intergeneric

microorganism’’ to clarify that

microorganisms which contain

introduced genetic material consisting

only of well-characterized, non-coding

regulatory regions from another genus

are not considered intergeneric for the

purposes of TSCA section 5. EPA agrees

with a commenter who suggested that

the regulations should have a single

definition of well-characterized and that

the definitions of ‘‘well-characterized’’

at §§ 725.3 and 725.421(b) should be

identical. To achieve this end, the

phrase ‘‘well-characterized, non-coding

regulatory region’’ would be deleted

from §§ 725.3 and ‘‘well-characterized’’

and ‘‘non-coding regulatory region’’

would be separately defined. Therefore,

the definition of ‘‘well-characterized,

non-coding regulatory region’’ is being

deleted and definitions of ‘‘non-coding

regulatory region’’ and ‘‘wellcharacterized’’ are being added to

§ 725.3. EPA agreed with the

commenter’s suggestion to use the

language in § 725.421(b) to define ‘‘wellcharacterized.’’ EPA developed the

definition of ‘‘non-coding regulatory

region’’ based on language pertinent to

the non-coding aspect of the definition

of ‘‘well-characterized, non-coding

regulatory region.’’ EPA believes that it

is necessary to specifically require that

the regulatory regions be non-coding. As

stated in the 1986 policy statement and

in the proposed rule, EPA excluded

from the definition of intergeneric

microorganisms, those microorganisms

that solely contained intergeneric

regulatory regions that are wellcharacterized and non-coding. Such

intergeneric material would not

introduce distinctly new combinations

of traits. Instead, only the level of

expression of existing traits in the

recipient microorganisms may be

altered. By also including a restriction

that the flanking sequences be noncoding, EPA is ensuring that persons

will consider the nature of the flanking

sequences associated with regulatory

regions when determining their

eligibility for the well-characterized,

non-coding regulatory region exclusion.

In the proposed rule, EPA indicated

that it may choose to reconsider its

interpretation of ‘‘new’’ microorganism

at a later time and in a separate

rulemaking. Of the 17 comments

received on scope of oversight, only 4

commenters strongly opposed the

intergeneric scope and supported

another approach, while 13 commenters

expressed some level of support for

intergeneric, albeit with some

modifications. EPA believes that while
17916 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

the intergeneric scope is not perfect, as

one commenter noted, ‘‘no one has

proposed a clearly superior scope,

despite years of discussion and debate.’’

Therefore, EPA is retaining the

intergeneric interpretation for the final

rule. However, EPA appreciates the

many useful suggestions made by

commenters for refinement of the

intergeneric interpretation and plans to

consider at a later time modifications to

the intergeneric interpretation,

including issues related to the exclusion

of well-characterized, non-coding

regulatory regions and to the MGE

policy. TSCA applicability and scope of

oversight are discussed in detail in the

proposed rule and in the Response to

Comments document in Unit II.

B. Reporting General Commercial Use of

Microorganisms

1. MCAN and SNUR. The final rule

incorporates many procedures that were

originally developed for the TSCA

section 5 program for traditional

chemicals. Procedures from parts 720

(premanufacture notification (PMN))

and 721 (significant new use

notification SNUN)) are being placed in

the new part 725 with the minor

modifications necessary to

accommodate the specific

characteristics of microorganisms. In

lieu of the PMN or SNUN described in

parts 720 and 721, respectively, EPA is

including in part 725 a requirement for

submission of a MCAN by persons who

intend to manufacture or import new

living microorganisms, and by persons

who intend to manufacture, import, or

process microorganisms for a significant

new use. Subpart D of part 725, which

contains the MCAN requirements, is

being promulgated without substantive

revision. The MCAN process is

discussed in the proposed rule and in

the Response to Comments document in

Unit III.A.

EPA received general comments about

the process, as well as specific

comments about contract

manufacturing, certain information

requirements for the MCAN process,

and the inclusion of requirements for

byproducts. EPA is providing additional

explanations and clarifications to

address these concerns. Both the

comments and EPA’s responses are

discussed in detail in the Response to

Comments document in Unit III.A.

In response to the commenters who

stated that the information required to

be submitted in the MCAN was

confusing, burdensome, and openended, EPA notes that both the

proposed and final rule require

submission only of the information that

is explicitly required to be submitted by

TSCA section 5(b) and 5(d)(1). The

purpose of the MCAN is to supply EPA

with information necessary to identify

and list the new microorganism on the

TSCA Inventory and to determine

whether the microorganism and the

associated activities would pose an

unreasonable risk of injury to human

health or the environment. The MCAN

information requirements closely

parallel those for PMNs and differ only

to the extent necessary to accommodate

the specific characteristics of living

microorganisms. Therefore, the

introductory paragraphs in § 725.155

have been revised to more closely

parallel the introductory language in

§ 720.45, which contains the

information requirements for the PMN.

EPA has also revised § 725.155(b) to

explicitly include the statement that the

submitter should include all reasonably

ascertainable information that will

permit EPA to make a reasoned

evaluation of the health and

environmental effects of the

microorganism. EPA believes that the

addition of the statement in § 725.155(b)

also addresses the commenter who

requested that EPA relate the

information requested to the data

necessary to assess potential risk to

human health and the environment.

The proposed subpart L of part 725

incorporated the Significant New Use

Rule (SNUR) provisions from part 721

with minor modifications to

accommodate the specific

characteristics of living microorganisms.

EPA is promulgating subpart L in the

final rule with minor revisions,

primarily to clarify the relationship of

subpart L to the other subparts in part

725. EPA has not yet proposed a SNUR

for a specific microorganism. EPA has

clarified its approach to microorganism

SNURs in response to commenters. The

SNUR for microorganisms is discussed

in the proposed rule (59 FR 45552-53)

and in the Response to Comments

document in Unit III.B.

2. Tiered exemption. EPA is

establishing under TSCA section 5(h)(4),

the Tier I and Tier II exemptions for

certain microorganisms meeting certain

criteria. The criteria defining eligibility

for the Tier I exemption address: (1) The

recipient microorganism; (2) the

introduced genetic material; and (3)

physical containment conditions to

minimize the numbers of

microorganisms emitted from the

manufacturing facility. For the Tier II

exemption, only the first two of the Tier

I criteria must be met. Manufacturers

would select containment appropriate to

minimize release of the microorganisms.

EPA would review the appropriateness

of the containment for the

microorganisms in an expedited 45–day

review. The requirements for the tiered

exemptions are found in subpart G of

part 725. In response to comments, EPA

has made certain revisions to

requirements for the introduced genetic

material at § 725.421 and for physical

containment at § 725.422. These are

discussed below. The tiered exemption

is discussed in detail in the proposed

rule (59 FR 45545-50) and in the

Response to Comments document in

Unit III.C.

a. General comments. EPA received

comments on issues related to the

overall approach to the tiered

exemption. While EPA did not make

substantive changes to the process for

the Tier I and Tier II exemptions, EPA

did make minor changes in §§ 725.424

through 725.470 to further clarify

exemption requirements. In Unit III.C.

of the Response to Comments

document, EPA provided additional

explanation of its rationale for

development of the tiered approach.

Some commenters indicated that it is

‘‘excessive and unwarranted’’ to require

the submitter for a tiered exemption to

certify that test data are being submitted

as stated in § 725.25(b). Another

commenter stated that a 30–day review

was not necessary and that companies

working with organisms eligible for the

Tier I exemption should simply

document their eligibility in their

records.

EPA wishes to clarify how the

certification statement at § 725.25(b)

applies to the tiered exemption. The

first two sentences, where the company

indicates that it intends to manufacture

the microorganism identified in the

submission and that all information is

complete and truthful, are applicable to

all submitters. However, the last

sentence is only relevant to persons

preparing either the MCAN which

includes information requirements at

§ 725.160 or the TERA which includes

information requirements at § 725.260.

To reduce confusion, EPA has added a

clarification to § 725.424(b)(5). EPA

inadvertently neglected in the proposed

regulatory text, although the proposed

preamble clearly describes procedures,

to include the requirements at

§ 725.424(b)(4) and (5) as requirements

for the Tier II exemption at § 725.455.

Therefore, EPA has added those

requirements as § 725.455(e) and (f) in

the final rule. Although § 725.25(b)

states that persons submitting

exemption requests must submit the

certification statement, EPA has

repeated the requirement at

§§ 725.424(b)(5) and 725.455(f) for the

convenience of submitters. The

requirement at § 725.455(e) was
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17917

inadvertently left out of the proposed

rule; however, EPA does not believe that

this requirement adds an additional

burden, because submitters should

already have information about waste

disposal of the microorganisms.

EPA agrees that EPA review is not

required for the Tier I exemption, as

EPA has already made the no

unreasonable risk finding for

microorganisms meeting the conditions

of the exemption. EPA has structured

the Tier I exemption such that EPA

receives a one-time certification alerting

EPA to the application of the exemption

and to demonstrate that the submitter is

complying with the criteria set out for

the exemption. The certification

contains no data for EPA to review.

Once a person has sent in the

certification required by § 725.424,

subsequent uses of the same recipient

do not require additional certification

under § 725.424, as long as the

manufacturer is continuing to comply

with the introduced genetic material

requirements of § 725.421 and the

containment requirements of § 725.422.

While EPA does not believe that an EPA

review is necessary, EPA does believe

that it is appropriate for EPA to be

notified of which manufacturers are

eligible for and utilizing the exemption.

However, EPA also has decided that

since the purpose of the certification is

solely to inform EPA that persons are

using the Tier I exemption, such

notification is not needed 30 days in

advance, and 10 days in advance of

manufacture or import is sufficient.

Therefore, EPA has revised the

requirement at § 725.424(a)(4) to require

submission of the certification to EPA at

least 10 days before commencing initial

manufacture or import of a new

microorganism.

b. Recipient microorganism. EPA

received no substantive comments

challenging EPA’s approach to selecting

recipient microorganisms for listing or

questioning the eligibility of the 10

candidates proposed for listing.

Therefore, EPA has not made

substantive changes to its approach to

selecting recipient microorganisms.

Section 725.420 continues to list the 10

microorganisms as eligible for use in the

tiered exemption. Although EPA

explained in detail in the proposal (59

FR 45545-47) the considerations it

evaluated in selecting candidate

microorganisms for listing at § 725.420,

EPA provided commenters with

additional explanation as to how six

criteria are used together to determine a

microorganism’s eligibility for listing at

§ 725.420. The recipient microorganism

criteria are discussed in detail in the

proposed rule (59 FR 45545-47) and in

the Response to Comments document in

Unit III.C.2.

Some commenters were concerned

about the effect of potential changes in

microbial taxonomy on the

microorganisms listed at § 725.420. The

risk assessments that EPA prepared for

the 10 microorganisms listed at

§ 725.420 evaluated the hazards of the

microorganisms as they were

appropriately designated taxonomically

in 1994. Therefore, EPA believes that if

in the future the name is changed for

any of the 10 microorganisms currently

listed in § 725.420, persons would need

to document that their microorganisms

would have been classified in 1994

under the name listed in § 725.420.

EPA proposed the petition process at

§ 725.67 to provide a mechanism for the

public to propose additional candidates

and provide the appropriate supporting

information. As a general matter, EPA

expects that petitions to add specific

recipient microorganisms to the list at

§ 725.420 will ideally be preceded by

several MCANs before the necessary

experience with and information on the

microorganism have been accumulated

to provide EPA with a starting point for

determining whether the recipient

should be listed as a candidate for the

tiered exemption. EPA has revised the

regulatory text for the petition process at

§ 725.67 generally to clarify that the

information required to be submitted in

a petition will mirror the information

requirements for the provision for

which the exemption is being sought.

With regard to the tiered exemption,

EPA has indicated at § 725.67(a)(3)(iii)

that when applying to list a recipient

microorganism for the tiered exemption

under § 725.420, persons should include

information addressing the six criteria,

which EPA will use to evaluate the

microorganism for listing. EPA made the

generic revision, because the petition

process was designed to be used by

anyone seeking to apply for a section

5(h)(4) exemption from full MCAN

reporting under TSCA section 5.

One commenter asked EPA to clarify

whether the microorganism Bacillus

amyloliquefaciens would be considered

a variant of the listed candidate Bacillus

subtilis and thus eligible for the tiered

exemption. EPA does not believe that

Bacillus amyloliquefaciens can be

subsumed under the exemption for

Bacillus subtilis. B. amyloliquefaciens

may have been considered a variant of

B. subtilis in the past; however, by the

time the risk assessment for B. subtilis

was developed in 1994, B.

amyloliquefaciens had been given

separate species status (Ref. 1).

Therefore, B. amyloliquefaciens is not

synonymous with B. subtilis, and EPA is

not including the former under the

exemption for the latter.

Another commenter asked that EPA

add Pseudomonas fluorescens to the list

at § 725.420. After review of the

information supplied by the commenter,

and other information referenced in the

Response to Comments Document in

Unit III.C.2.b., EPA has concluded that

the species P. fluorescens is not eligible

for listing as a recipient microorganism

under § 725.420 at this time for the

following reasons: its confusing

taxonomic status; its lack of history of

safe commercial use; and the potential

of some strains currently classified as P.

fluorescens to cause adverse effects on

human health and the environment,

particularly in relation to plant

pathogenicity. EPA’s review does not

represent a full consideration of the

species P. fluorescens, because

sufficient information was not

submitted. Thus EPA responds to the

commenter’s request as a rule comment

and not a formal petition.

c. Introduced genetic material. For the

introduced genetic material, EPA

identified four requirements in

§ 725.421 which must be met to qualify

for the Tier I or Tier II exemptions: the

genetic material must be (a) limited in

size, (b) well-characterized, (c) poorly

mobilizable, and (d) free of certain

sequences. EPA responds to comments

on the criteria for the introduced genetic

material within the context of the

intergeneric scope. The terms in the

final regulatory text for the tiered

exemption refer to ‘‘introduced genetic

material’’ and only the intergeneric

portions of the introduced genetic

material must meet the requirements at

§ 725.421. Therefore, the requirements

in § 725.421 refer solely to the

introduced genetic material which is

derived from an organism classified in

a different genus from the recipient

microorganism. The introduced genetic

material criteria are discussed in detail

in the proposed rule (59 FR 45547-48)

and in the Response to Comments

document in Unit III.C.3.

(i) Limited in size. The requirements

for the ‘‘limited in size’’ criterion are set

forth at § 725.421(a), which states that

the introduced genetic material must

consist only of the following: (1) The

structural gene(s) of interest; (2) the

regulatory sequences permitting the

expression of solely the gene(s) of

interest; (3) associated nucleotide

sequences needed to move genetic

material, including linkers,

homopolymers, adaptors, transposons,

insertion sequences, and restriction

enzyme sites; (4) nucleotide sequences

needed for vector transfer; and (5)

nucleotide sequences needed for vector
17918 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

maintenance. EPA discussed its

rationale supporting the limited in size

criterion in the preamble to the

proposed rule (59 FR 45547).

EPA is providing additional guidance

for interpreting the ‘‘limited in size’’

requirements in this preamble and in

the Response to Comments document in

Unit III.C.3.a., but is not making changes

to the regulatory text at § 725.421(a).

Commenters generally requested that

EPA clarify which vector sequences

would meet the criterion, including the

status of certain sequences found in

well-known, frequently used plasmids.

In response, EPA is clarifying that it

interprets requirement (3) above to

allow the introduced DNA to contain

vector material necessary for

maintenance in and/or transfer to

intermediate hosts, provided this vector

material is not expressed in the

intergeneric microorganism that will be

manufactured under the tiered

exemption. Such nonexpressed vector

material should not change the behavior

of the intergeneric microorganism. EPA

also indicates that certain plasmid and

phage vectors listed in Appendices E

and I of the National Institutes of Health

Guidelines for Research Involving

Recombinant DNA Molecules (NIH

Guidelines (59 FR 34496, July 5, 1994)

(FR Doc. 94–16200)) (Ref. 2) would meet

the introduced genetic material criteria

including the limited in size criterion.

(ii) Well-characterized. The

requirements for the ‘‘wellcharacterized’’ criterion are set forth at

§ 725.421(b) which states that well

characterized means that the following

have been determined for the

introduced genetic material: (1) The

function of all of the products expressed

from the structural gene(s); (2) the

function of sequences that participate in

the regulation of expression of the

structural gene(s); and (3) the presence

or absence of associated nucleotide

sequences where associated nucleotide

sequences are defined as those ‘‘needed

to move genetic material, including

linkers, homopolymers, adaptors,

transposons, insertion sequences, and

restriction enzyme sites.’’ EPA

discussed its rationale supporting the

well-characterized criterion in the

preamble to the proposed rule (59 FR

45547).

EPA is providing additional guidance

for interpreting the ‘‘well characterized’’

requirements in this preamble and in

the Response to Comments document in

Unit III.C.3.b., but is not making

changes to the regulatory text at

§ 725.421(b). Commenters expressed

concerns about what it means to know

the functions of all products expressed

by the structural genes, how to address

open reading frames (ORFs) present in

the introduced genetic material, what

information is needed to determine

whether upstream activator sequences

meet the ‘‘well-characterized’’ criterion,

and whether complete genomic

sequencing of the final construct is

necessary to meet the well-characterized

definition.

EPA’s intent in developing the ‘‘wellcharacterized’’ criterion was to ensure

that the functions introduced with the

genetic material were sufficiently

understood to predict the likely

behavior of the resulting microorganism.

Because EPA defined a ‘‘new’’

microorganism as an intergeneric

microorganism, it is the predicted effect

of the intergeneric sequences on the

phenotype of the recipient

microorganism that must be evaluated.

With regard to the functions of products

expressed by introduced structural

genes, manufacturers could rely, for

example, on peer-reviewed literature on

products of structural genes and/or the

results of protein expression assays to

characterize the function(s) of a gene

product.

Manufacturers must ensure, by

evaluating ORFs and multiple reading

frames, that unanticipated novel traits

are not expressed by the intergeneric

microorganism. ORFs must be assessed

to determine whether a product other

than the anticipated, desired product is

likely to be expressed and to predict

whether such a product(s), if expressed,

would have an effect on the phenotype

of the intergeneric microorganism.

In determining the status of upstream

activator sequences (UASs) with regard

to the exemption at § 725.421,

manufacturers must first consider

whether introduction of the UAS would

create an intergeneric microorganism.

For a UAS isolated from an organism in

a different genus from the recipient

microorganism, manufacturers should

determine whether their UAS meets the

requirements in the definitions at

§ 725.3 for ‘‘non-coding regulatory

region’’ and for ‘‘well-characterized.’’

Microorganisms developed through the

introduction of only UAS genetic

material that is isolated from an

organism in a different genus and that

meets the above-noted definitions at

§ 725.3, are excluded from the definition

of ‘‘intergeneric microorganism’’ and

therefore are not subject to the

requirements of TSCA section 5.

Manufacturers who wish to utilize the

tiered exemption for microorganisms

that contain both a UAS(s) and other

genetic material isolated from an

organism(s) in a different genus than the

recipient, must, to meet the exemption

requirements: (1) Ensure that the UAS

meets the definitions of ‘‘non-coding

regulatory region’’ and ‘‘wellcharacterized’’ at § 725.3; (2) ensure that

the other introduced genetic material

meets the requirements at § 725.421(b);

and (3) ensure that the other

requirements of the Tier I or Tier II

exemption are met.

(iii) Poorly mobilizable. The

requirements for the ‘‘poorly

mobilizable’’ criterion are set forth at

§ 725.421(c) which states that the

probability that the introduced genetic

material would be transferred to other

microorganisms must be low, with a

frequency of transfer of less than 10-8

transfer events per recipient. EPA

discussed its rationale supporting the

poorly mobilizable criterion in the

preamble to the proposed rule (59 FR

45547-48).

EPA is providing additional guidance

for interpreting the ‘‘poorly

mobilizable’’ requirements in this

preamble and in the Response to

Comments document in Unit III.C.3.c.,

but is not making changes to the

regulatory text at § 725.421(c). Some

commenters requested clarification on

the conditions under which the 10-8

criterion should be measured. They also

requested that EPA clarify the status

with regard to the ‘‘poorly mobilizable’’

criterion of introduced genetic material

located on the chromosome.

EPA believes the 10-8 criterion, which

is a standard established by NIH in its

Guidelines (Ref. 2) and an important

feature of the Good Industrial LargeScale Practices (GILSP) criteria

developed by the Organization of

Economic Cooperation and

Development (OECD) (Ref. 3), should be

applied to the introduced genetic

material under § 725.421, because EPA

is not restricting (aside from that under

§ 725.421(d)) the source and function of

the introduced genetic material.

Therefore, EPA in order to make the

finding that organisms meeting the other

criteria at § 725.400 present low risk, the

‘‘poorly mobilizable’’ standard must be

included in the criteria at § 725.421.

EPA believes that manufacturers can

readily determine whether the

introduced genetic material will meet

the 10-8 criterion. For many bacteria,

most sequences introduced by

transduction and transformation will a

priori meet the 10-8 criterion. Therefore,

a single mechanism of gene exchange,

conjugation, will need to be considered

and the introduced genetic material

constructed to meet the 10-8 standard for

that mechanism. EPA also clarifies that

genetic material stably integrated into

the chromosome with no functional

transposons is likely to meet the 10-8

criterion.
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17919

(iv) Free of certain sequences. The

requirements for the ‘‘free of certain

sequences’’ criterion were set forth at

proposed § 725.421(d) which indicated

that the introduced genetic material

must not contain any part of the

nucleotide sequences that encode

certain listed toxins, which are

polypeptides of relatively high potency.

EPA discussed its rationale supporting

the ‘‘free of certain sequences’’ criterion

in the preamble to the proposed rule (59

FR 45547).

A commenter noted that the language

in proposed § 725.421(d), if taken

literally, would ‘‘preclude the use of

DNA that codes for a pair of amino acids

(or even a single one) if that sequence

also occurs in any of these toxins.’’ In

order to clarify this point, the

commenter suggested that the language

be altered to state that the introduced

genetic material must not contain a

sequence ‘‘encoding any active moiety

of a toxin’’ listed in § 725.421(d).

EPA is providing additional guidance

for interpreting the ‘‘free of certain

sequences’’ requirements in its

Response to Comments document in

Unit III.C.3.d., and is modifying the

regulatory text at § 725.421(d) to clarify

its intentions. The introductory text of

§ 725.421(d) has been modified to

include the term ‘‘functional portion of

a toxin-encoding sequence.’’ To assist

submitters in interpreting the term

‘‘functional portion’’ of a toxin-encoding

sequence described at § 725.421(d), EPA

provides a discussion of sequences that

directly or indirectly contribute to toxic

effects in human cells. For toxins that

affect a cell’s cytoplasmic functions,

nucleic acid sequences that encode the

‘‘functional portion’’ of a toxin are those

which encode either functional receptor

binding or toxic domains of the toxin.

For toxins that affect a cell’s membrane,

nucleic acid sequences that shall not be

included in the introduced genetic

material are those which encode the

functional portion that allows target cell

membrane disruption.

EPA did not intend for the restriction

on toxin-encoding sequences to be

interpreted to mean that the presence of

a nucleotide found in a toxin gene

sequence on the list at § 725.421(d)

would preclude introduced genetic

material containing that nucleotide from

qualifying for the tiered exemption. EPA

believes the likelihood of any significant

risk resulting from incorporation of

nonfunctional portions of a toxin gene

into a recipient listed at § 725.420 is

low. EPA is also modifying the

definition to emphasize that EPA is

excluding specific toxin sequences and

not source organisms, which are listed

at § 725.421(d) to identify the toxins.

d. Physical containment. The

proposal included the following

containment requirements at § 725.422

for the Tier I exemption: (1) The

structure is designed and operated to

contain the microorganism, (2) limit

entry only to those persons whose

presence is critical to the reliability or

safety of the activity, (3) provide

written, published, and implemented

procedures for the safety of personnel

and control of hygiene, (4) provide and

document effectiveness of inactivation

procedures to reduce microbial

concentrations by at least 6 logs in

liquid and solid wastes, (5) provide and

document effectiveness of features to

reduce microbial concentration by at

least 2 logs in aerosols and exhaust

gases released from the structure, (6)

include and document systems for

controlling dissemination of the

microorganisms through other routes,

(7) have in place emergency clean-up

procedures. Most of the comments

focussed either on (2), the limited entry

requirement, or (4) and (5), the

inactivation requirements. The physical

containment criteria are discussed in

detail in the proposed rule (59 FR

45548-49) and in the Response to

Comments document in Unit III.C.4.

(i) Limited entry requirement. Some

commenters indicated that the limited

entry requirement was too restrictive,

given the low potential hazards posed

by microorganisms used under the Tier

I exemption criteria. Specifically, they

stated that under that requirement,

managers may be precluded from

allowing administrative personnel,

customers, school and other educational

tours into the facility. It was not EPA’s

intention to constrain facility managers

to this extent. Consequently, EPA

recognizes that language at proposed

§ 725.422(b) may have been stricter than

was necessary. Neither the NIH

Guidelines (Ref. 2) nor the OECD GILSP

criteria (Ref. 3) have specific limited

entry requirements for large scale uses

of comparable microorganisms.

Additionally, EPA’s review of PMNs

received for intergeneric

microorganisms indicated that restricted

entry was not common industry practice

(Ref. 4). EPA agrees with the

commenters who stated that given the

low risk posed by the microorganisms

eligible for the exemption, managers

should have the discretion to allow

administrative personnel, customers,

and school and other educational tours

into the facility. However, EPA also

expects that managers will maintain

appropriate containment, thereby

controlling access and avoiding

inadvertent exposure. Modification of

the language of this requirement does

not alter EPA’s original determination

that microorganisms that are eligible for

and used under the conditions of the

Tier I exemption will not present an

unreasonable risk of injury to human

health and the environment. Therefore,

EPA has revised § 725.422(b) to read

‘‘Control access to the structure.’’

(ii) Inactivation requirements. Some

commenters indicated that with the

limitations placed on the recipient

microorganism and the introduced

genetic material, quantitation of

inactivation procedures was not

necessary. The commenters stated that it

would be necessary to modify existing

equipment to sample off-gas as required

and that an additional sample port

would increase the potential for

contamination and worker exposure.

The commenters suggested that instead

of numerical requirements, language be

substituted that more generally required

reduction of microorganisms in liquid

and solid wastes and aerosols and

exhaust gases. Other commenters stated

that the numerical requirements for the

inactivation procedures are too lenient.

These commenters suggested that gases

be vented through a HEPA filter or

incinerated. They also recommended

that the containment criteria be

coordinated with the containment levels

set out in the NIH Guidelines (Ref. 2).

After considering comments regarding

its inactivation requirements at

proposed § 725.422(d) and (e), EPA

reviewed information submitted on

physical containment and control

technologies in PMNs it has received for

intergeneric microorganisms between

1986 and 1995 (Ref. 4). On the basis of

that review, EPA has made the

following determinations. EPA has

decided to retain § 725.422(d) which

requires the use of inactivation

procedures that reduce microbial

concentrations by at least 6 logs in

liquid and solid wastes. However, EPA

has determined that it is appropriate to

revise § 725.422(e) to read ‘‘Provide and

document effectiveness of features to

minimize viable microbial populations

in aerosols and exhaust gases released

from the structure.’’ The physical

containment criteria are discussed in

detail in the Response to Comments

document in Unit III.C.4.

As indicated in the preamble to the

proposed rule (59 FR 45548-49), EPA

believed that it was appropriate to

prescribe standards for minimizing the

number of microorganisms emitted

through the disposal of wastes, because

a wide range of behaviors could be

displayed by microorganisms eligible

for the exemption and because EPA

would not be reviewing MCANs on
17920 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

microorganisms eligible for the Tier I

exemption. EPA believes that the

requirement for a 6-log reduction in the

number of microorganisms is reasonable

for inactivation of liquid and solid

wastes and well within current industry

practices. The 6-log reduction criterion

represents a level of inactivation which

can be validated. This standard gives a

decrease in viable microbial populations

so that at least 99.9999 percent of the

organisms resulting from the

fermentation will be killed. EPA

discusses the application of this

standard under normal industry

practices in the proposed rule (59 FR

45548-49) and in the Response to

Comments document in unit III.C.4.b.

An examination of PMNs for

intergeneric microorganisms (Ref. 4)

revealed that this criterion is readily

achievable by manufacturers. The

review of these PMNs also indicated

that in the several cases where

monitoring was conducted there were

no detectable viable microorganisms in

liquid and solid wastes after

inactivation (Ref. 4). EPA believes that

the 6-log reduction in viable microbial

numbers in the liquid and solid wastes

is a reasonable and demonstrable

performance criterion ensuring an

appropriate level of containment for the

low risk microorganisms which would

be eligible for the tiered exemption.

As indicated in the preamble to the

proposed rule (59 FR 45548-49), EPA

believed that it was appropriate to

require manufacturers to minimize the

number of microorganisms emitted

through the venting of gases. A wide

range of behaviors could be displayed

by microorganisms eligible for the

exemption, and EPA would not be

reviewing MCANs for microorganisms

eligible for the Tier I exemption. In the

proposal EPA indicated that a 2-log

reduction in viable microorganisms per

cubic foot of air between the headspace

and the actual vent port was the

appropriate standard. EPA chose this

number based on an estimate of the

numbers of microorganisms likely to be

in the exhaust from an uncontrolled

fermentor and common industry

practice. EPA discusses the application

of this standard under normal industry

practices in the proposed rule (59 FR

45549) and in the Response to

Comments document in unit III.C.4.b.

Additionally, the 2-log reduction

represented a somewhat less restrictive

number than the reduction obtained

with HEPA filter filtration (the

reduction level required for the NIH

Guidelines BL1-LS level (NIH,

Appendix K, 1995) (Ref. 2).

However, EPA received several

comments pointing out the technical

problems associated with the proposed

2-log reduction performance criterion.

EPA agrees with the commenters that

companies should not have to modify/

retrofit their existing equipment nor

jeopardize the sterility of their

fermentations in order to validate that

the number of microorganisms being

released in the exhaust has been

reduced by at least 2 logs relative to the

microbial numbers in the fermentor

gases in the headspace. EPA did not

intend that retrofitting or any other

burdensome engineering modifications

would be necessary for those who

wished to utilize the Tier I exemption.

Rather, EPA had intended to develop

requirements for this exemption that

would impose performance standards

for equipment already commonly used.

In light of comments received, EPA has

sought to modify its requirement to

achieve its goal of having submitters

demonstrate that the equipment or

features normally employed in

fermentation systems are effective in

reducing numbers of viable

microorganisms being vented in exhaust

gases.

As stated in the preamble and noted

by commenters, industrial fermentations

are not routinely run in an uncontrolled

fashion, and thus the number of

microorganisms potentially released

into the gas phase and unrecovered is

controlled. Additionally, an

examination of PMNs for intergeneric

microorganisms (Ref. 4) showed that all

of the fermentations, which were

operating under standard industry

practices, were utilizing features which

minimize the number of

microorganisms released in the offgases.

For fermentations to operate

optimally, vapor recovery systems are

used to maintain the correct growth

conditions for the microorganisms, e.g.,

correct molality in the fermentation

broth must be maintained. Vapor

recovery systems, by their nature, help

to minimize the number of

microorganisms exhausted from the

facilities. EPA believes that it should

allow some flexibility in the type of

features manufacturers employ to

minimize microbial releases as aerosols.

A variety of fermentor equipment or

features are commonly used by the

industry such as demisters, wet

scrubbers, cyclone separators,

coalescing filters, and HEPA filters.

These types of equipment reduce the

number of microorganisms vented

through exhaust gases from the

fermentor. Moreover, as stated in the

preamble (59 FR 45549), even if

microorganisms are exhausted from the

fermentor, their survival is likely to be

limited due to the stress conditions of

aerosolization, including shear forces,

desiccation, and UV light exposure.

Given the comments received on the

feasibility of this requirement and the

variety of methods used by PMN

submitters to reduce microbial numbers

in aerosols, EPA believes that a specific

numerical performance standard is less

appropriate for inactivation of aerosols

than it is for inactivation of liquid and

solid wastes. EPA agrees with

commenters who asserted that the

majority of microorganisms potentially

released from the fermentation facility

would be found in the liquid and solid

wastes. EPA has prescribed a specific

viable microorganism reduction

standard for these materials. Therefore,

EPA believes that if the new

microorganism meets all of the other

requirements of the Tier I exemption, it

is sufficient to require use of validated

methods for minimizing release of

microbial concentrations in aerosols and

exhaust gases without prescribing a

specific numerical reduction in

numbers. If manufacturers are

conducting their quality assurance/

quality control (QA/QC) monitoring to

ensure proper performance of their

fermentation equipment, EPA believes

that the facilities would be meeting the

requirement of § 725.422(e). EPA has

revised § 725.422(e) to read: ‘‘Provide

and document effectiveness of features

to minimize viable microbial

populations in aerosols and exhaust

gases released from the structure.’’

Based on the above points and the

results of the review of EPA’s PMN

experience, EPA believes that this

requirement will ensure that the number

of microorganisms released in fermentor

off-gases will be negligible and allow

EPA to make the ‘‘no unreasonable risk’’

finding of section 5(h)(4).

EPA does not agree with commenters

who stated that a 2-log reduction for

aerosols is too lenient. As discussed in

the proposed rule (59 FR 45549), even

if small numbers of microorganisms are

released in fermentor exhaust gases,

aerosolization is a stressful condition

decreasing the survival of most

microorganisms. Aerosolized bacterial

cells are weakened by shear forces, and

are subject to desiccation and exposure

to UV light. Therefore, survival of

aerosolized microorganisms is expected

to be limited. Since organisms which

are eligible as recipient microorganisms

for the Tier I exemption are low risk,

EPA does not believe it is necessary to

impose more stringent conditions than a

requirement that manufacturers

minimize the numbers of

microorganisms in fermentor off-gases.
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17921

Several commenters suggested that

EPA coordinate its containment criteria

with those specified in the NIH

Guidelines (Ref. 2). EPA considered use

of the NIH Guidelines when it was

developing the tiered exemption but

found such an approach to be

problematic. In particular, the NIH

Guidelines may change through a

process independent of EPA activities

such that the Guidelines would no

longer provide the appropriate criteria

to support a TSCA section 5(h)(4)

exemption. EPA has developed an

approach at § 725.422 based, in large

part, on standards set forth in the NIH

Guidelines and the OECD GILSP that

allow EPA to make the finding that is

required under TSCA section 5(h)(4).

However, in considering the specific

containment requirements of the current

NIH Guidelines (Ref. 2), EPA could not

find one level in Appendix K that EPA

believed would be appropriate for the

Tier I exemption. The NIH Good Large

Scale Practice (GLSP) criteria that

would be applicable to some, but not

all, of the microorganisms listed at

§ 725.420, do not require minimization

of the numbers of microorganisms

released in off-gasses. Biosafety Level 1-

Large Scale (BL1-LS) criteria require the

use of HEPA filters or their equivalent,

a 3-log reduction, and therefore are

more restrictive than EPA’s original 2-

log reduction requirement.

In reconsidering its original

requirement, EPA believes that the costs

of retrofitting existing equipment as

well as the increase in potential

contamination and worker exposure that

would accompany sample collection

necessary to validate the 2-log reduction

requirement are not justified for the low

risk microorganisms eligible for the

exemption. EPA has attempted to make

its approach compatible with good

practice in industry. Most of the

requirements of § 725.422 are analogous

to NIH Guidelines requirements. In

particular, companies who are in full

compliance with the NIH BL1-LS

requirements would also be in

compliance with § 725.422(e), although

the use of HEPA filters or their

equivalent is a more stringent

requirement than § 725.422(e).

C. Reporting R&D Activities of

Microorganisms

As discussed earlier in this preamble

and in the proposed rule, TSCA section

5 generally requires notification to EPA

at least 90 days prior to the manufacture

and importation of new chemical

substances and 90 days prior to the

manufacture, importation, and

processing of designated chemical

substances for significant new uses.

TSCA section 5(i) makes clear that only

manufacturing, importing, and

processing ‘‘for commercial purposes’’

are subject to section 5 notification.

TSCA section 5(h)(3) exempts entirely

from notification under section 5 the

manufacturing, importing, and

processing of chemical substances ‘‘only

in small quantities (as defined by the

Administrator)’’ for R&D, subject only to

the manufacturer, importer, or processor

notifying (as prescribed by EPA) the

persons involved in the R&D activity of

any risks to health associated with the

substance.

As discussed in more detail below, for

traditional chemical substances, EPA

has defined ‘‘small quantities’’ for R&D

to be those quantities ‘‘not greater than

reasonably necessary’’ for the R&D

purposes. However, EPA is adopting a

different definition of ‘‘small quantities’’

for R&D for microorganisms, because

living microorganisms may reproduce

and increase their own volume or

amount. The definition adopted in this

final rule limits the section 5(h)(3)

exemption from section 5 MCAN

requirements to R&D activities that are

adequately contained as set forth in

§ 725.234.

This narrower definition of ‘‘small

quantities’’ means that R&D activities

conducted outside the prescribed

containment (including field tests) do

not qualify for the section 5(h)(3)

exemption and are subject to the MCAN

requirement. However, EPA has created,

under authority of TSCA section 5(h)(4),

other exemptions that will reduce the

reporting burden for persons conducting

certain R&D activities that do not

qualify for the complete exemption in

section 5(h)(3). These activities are

discussed below.

Researchers, including those in

academic institutions, may be subject to

TSCA section 5 jurisdiction because, by

creating or reproducing microorganisms

in their R&D activities, they are

‘‘manufacturing’’ or ‘‘processing’’ such

microorganisms. Since many such R&D

activities involving microorganisms will

not qualify for the section 5(h)(3)

exemption from MCAN reporting, it is

important for researchers, including

those in academic institutions, to

determine whether their activities fit

within the definition of ‘‘commercial

purposes’’ and, thus, are subject to

TSCA section 5 and the MCAN

requirements at all. Because of the

nature of microorganism R&D and the

broad definition of ‘‘commercial

purposes’’ discussed below, it is likely

that many researchers, including some

in academic institutions, will be subject

to TSCA section 5 jurisdiction for the

first time and will want to utilize the

TERA and other exemption provisions

to reduce the reporting burdens

involved in their R&D activities.

Each of the exemptions for R&D

activities applies to specific types of

activities. At the beginning of R&D,

while the research is taking place in a

laboratory subject to appropriate

containment, the R&D activity may be

fully exempt under the section 5(h)(3)

exemption if the researcher complies

with the conditions set out in the rule.

Once the researcher decides to conduct

research outside the contained setting,

such as field tests, the researcher will

need to utilize a different exemption,

such as the TERA.

1. TSCA jurisdiction. EPA did not

propose any provisions that would alter

the jurisdictional scope of section 5, i.e.,

whether the use or potential use of a

microorganism would be subject to

TSCA. However, EPA received

comments asking for clarification

regarding TSCA section 5 coverage of

R&D activities with microorganisms. A

commenter requested clarification of

EPA’s statement that ‘‘EPA would

consider that R&D activities involving

new microorganisms where researchers

are unsure of the final use would be

subject to TSCA section 5.’’ Some

commenters requested that EPA confirm

that researchers working with new

microorganisms for the purposes of

developing products such as drugs and

foods would not be subject to TSCA

section 5.

EPA did not intend to imply that

researchers using microorganisms

would automatically be subject to

section 5 requirements, without

consideration of whether the research

was conducted for a commercial

purpose. The commenters apparently

misunderstood EPA’s proposed

preamble discussion, which was

intended only to explain the analytical

steps to follow in determining whether

researchers would be required to file a

TERA notice.

Researchers attempting to determine

potential TSCA section 5 obligations for

R&D activities would first ascertain

whether the use or potential use of the

microorganism is specifically excluded

from TSCA section 5. Uses that are not

specifically excluded are subject to

TSCA. EPA anticipates that much R&D

activity with microorganisms will not be

subject to TSCA. If the research is

conducted with the intention of

developing a product, the use of which

would be subject solely to the Federal

Food, Drug, and Cosmetic Act (FFDCA),

the research would not be subject to

TSCA. For example, with regard to

biotechnology companies engaged in

development of drugs, TSCA
17922 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

specifically excludes substances used in

the production of foods, drugs,

cosmetics and medical devices from

TSCA jurisdiction. Microorganisms

used in the production of foods, drugs,

cosmetics and medical devices are

similarly excluded from TSCA.

However, researchers unsure of the final

use or potential use, or who intend to

develop a product, a use of which could

be subject to either FIFRA or TSCA, will

need to consider whether they are

subject to TSCA. Further discussion of

the comments and EPA’s responses can

be found in the Response to Comment

document at Unit IV.A. If the research

is subject to TSCA, researchers may be

eligible for one of the exemptions

discussed in Units IV.C. and E. of the

Response to Comments document.

2. Commercial R&D. The most

substantial decision made in developing

the final rule was selection of the

definition of commercial purposes for

R&D activities. This issue is discussed

in detail in the proposed rule (59 FR

45537-39) and in the Response to

Comments document in Unit IV.B.

TSCA section 5(i) limits all section 5

screening to activities for commercial

purposes. Research on traditional

chemicals is not generally affected by

the commercial purposes limitation,

because EPA’s current regulatory

definition of small quantities for R&D

using traditional chemicals (any

amounts reasonably necessary for

research) at § 720.3 effectively exempts

most research with these chemicals

from section 5 review. However,

because of the ability of microorganisms

to reproduce, disseminate and spread,

EPA believed that it was necessary to

review these products at an earlier stage

and therefore proposed an interpretation

to address testing with microorganisms.

Consequently, EPA developed a

different small quantities definition for

microorganisms and is imposing

reporting and recordkeeping

requirements on certain R&D activities.

Researchers utilizing microorganisms,

therefore, will need to consider whether

their R&D activities would be

considered commercial, and therefore

subject to TSCA section 5 requirements.

During development of regulations on

biotechnology over the past several

years, EPA has received numerous

public comments that differ

substantially on how the Agency should

apply the commercial purposes

definition to research. Of particular

concern has been the appropriateness of

an EPA oversight system based on the

status of an activity as commercial or

noncommercial rather than on potential

risk. Because of the past difference in

public opinion, EPA proposed three

approaches to defining what constitutes

commercial activities: (1) Using indicia

to determine commercial purposes; (2)

presuming all environmental testing is

commercial; and (3) presuming that all

environmental research is commercial

but offering an opportunity for

researchers to rebut the presumption.

Rather than indicating a preference,

EPA discussed in the preamble the

advantages and disadvantages of each

approach and asked for public comment

on which approach would be

appropriate.

Comments received on the proposed

rule produced no prevailing opinion on

how EPA should define ‘‘commercial

purposes’’ for R&D. In considering this

issue, EPA turned to its experience over

the past several years responding to

researchers who inquired about the

status of their field tests under TSCA.

EPA based its responses to those

inquiries, in part, on its approach to

traditional chemicals under TSCA.

Under the TSCA section 5 program for

traditional chemicals, EPA determines

whether an activity is for a commercial

purpose based on whether the purpose

of the activity is to have an immediate

or eventual commercial advantage. EPA

found that determining the commercial

status of research microorganisms based

on indicia similar to those used for

traditional chemicals functioned

adequately. Therefore, EPA has decided

that for this final rule when determining

whether their R&D activities with

microorganisms would be ‘‘for

commercial purposes,’’ researchers will

need to consider the indicia listed in

§ 725.205(b).

The indicia approach applies to R&D

in laboratories and other contained

structures as well as to intentional

testing in the environment and is

discussed in more detail below.

Researchers who are attempting to

determine whether their research would

be for ‘‘commercial purposes’’ should

consult § 725.205(b). Under

§ 725.205(b)(1) researchers would first

consider whether any of the funding for

the proposed research comes directly

from a commercial source. Any direct

industry involvement in or direct

funding of an activity at a

noncommercial institution is for

commercial purposes. This would

include the use of company funds to

develop the microorganisms or the use

of a company-provided microorganism

in the research. If any portion of the

research is funded directly by a

commercial source, then the research is

‘‘for commercial purposes.’’ Thus, if any

part of the research is funded by

contract, joint venture, or other financial

arrangement, with the purpose of

eventually producing a commercial

product, the research is subject to the

requirements of section 5. For example,

laboratory work or field tests conducted

under a research contract between a

company and a university or a

researcher where patent rights or trade

secrets are held by the company, would

be considered commercial R&D.

If researchers do not fall under

§ 725.205(b)(1), they should next

consider potential indirect indicators of

commercial intent as reflected in

§ 725.205(b)(2). They would need to

consider, for example, whether the

research is directed towards developing

a commercially viable improvement of a

product already on the market, or

whether they are seeking commercial

funding or a patent.

If researchers do not fall within the

scope of § 725.205(b)(1) or (b)(2), their

research may be considered

noncommercial. For example, an

outright gift from a company to a

university or a researcher without the

company directing or otherwise

controlling the research for which the

funds are to be used or the use to be

made of the results of the research

conducted, would not be considered

direct funding under § 725.205(b)(1). As

such, the research conducted using such

a gift would be considered

noncommercial R&D, assuming the

researcher also does not believe the

microorganism has the potential to be

developed as a commercial product in

the future or intend to obtain an

immediate or eventual commercial

advantage as described under

§ 725.205(b)(2). Therefore, if a

researcher is planning to conduct

laboratory work or field tests or other

environmental testing using funds

which were part of an outright gift from

a company to the university with no

strings attached, that research would be

considered noncommercial R&D.

If none of the funding or support for

the laboratory work or field test or other

environmental testing, including

development of the microorganism,

comes from a commercial source, then

the researcher must consider whether he

or she intends to pursue the

development of the new microorganism

as a commercial product in the future,

should testing show potential

commercial viability. The researcher is

responsible for judging when

commercial intent exists for his or her

particular research project. EPA

recognizes that in the initial stage of

research projects, researchers may not

envision an eventual commercial

purpose for their microorganisms.

However, if, during the course of their

investigations, researchers determine
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17923

that their microorganism has a potential

commercial use which they intend to

pursue, they then become subject to the

requirements of TSCA section 5 and this

rule, and their further research activities

must be in compliance with this rule.

EPA has provided examples of research

that has an immediate or eventual

commercial advantage in the regulatory

text at § 725.205(b)(2)(i) through (iv). An

example of ‘‘other evidence’’ of a

commercial application cited under

§ 725.205(b)(2)(iv) would be if the

researcher has engaged in serious

discussions with a company concerning

marketing or commercializing the

microorganism if initial research is

successful. If researchers have difficulty

deciding whether their research is for

commercial purposes, they are

encouraged to consult EPA.

The above approach represents a

modified version of the indicia of

commercial purposes approach

discussed in the preamble to the

proposed rule. EPA has adopted this

modified version for the following

reasons. All research conducted directly

by a commercial entity is clearly for

commercial purposes, as the court

decided in The Dow Chemical Company

v. EPA, 605 F.2d 673 (3d Cir. 1979).

Consequently, if a business directly

funds a research activity for potential

product development, the activity is for

commercial purposes, even if the

research activity is conducted at an

academic institution. EPA has chosen to

focus on the source of funding for the

specific laboratory work or field test or

other environmental testing as the

appropriate indicator of commercial

intent, because EPA recognizes that it

can be difficult to trace sources of

funding at the institutional level and

agrees with the commenter who stated

that ‘‘there is no logical basis for the

assertion that commercial support of

one narrowly defined project changes

the fundamental academic nature of

every other activity conducted

elsewhere in the institution.’’

EPA’s definition of commercial

purposes is consistent with the current

regulations for traditional chemicals,

which define a commercial activity as

one undertaken with the purpose of

obtaining an immediate or eventual

commercial advantage. For example,

this is the definition in § 720.3(r), which

defines ‘‘manufacture or import for

commercial purposes,’’ and § 721.3,

which defines ‘‘process for commercial

purposes.’’ Consequently, EPA has

adopted the idea in § 725.3, which

defines for microorganisms

‘‘manufacture, import, or process for

commercial purposes.’’ Similarly,

§ 720.30(i) provides that ‘‘noncommercial research and development’’

consists of activities conducted by

academic, government, or independent

not-for-profit organizations ‘‘unless the

activity is for eventual commercial

purposes.’’ EPA has developed a

comparable exclusion for noncommercial R&D uses of

microorganisms by including a

definition of ‘‘commercial purposes for

research and development activities’’ at

§ 725.205(b). As noted above, this

commercial indicia approach applies to

R&D in laboratories and other contained

structures, as well as to intentional

testing in the environment.

EPA’s experience over the past several

years responding to researchers

inquiring about the status of their

environmental research under TSCA

indicates the following points. All of the

researchers identified the sources of

their funding for the particular

experiments. Generally they were able

to readily indicate whether they

believed there was a future commercial

application for the microorganism

which they intended to pursue. In most

cases where a company was directly

funding field tests to be conducted at

university sites, the company contacted

EPA directly and took responsibility for

preparation of the PMN. In one case,

researchers were being funded by

Federal agencies but were using

company-owned microorganisms

subject to a TSCA section 5(e) consent

order. The company asked EPA to

modify the consent order to allow the

company to give the microorganisms to

the researchers for use in their field

tests. Although the company made the

original request, the researchers

submitted information about their field

tests to EPA. Therefore, researchers

should contact EPA if they are planning

field tests involving intergeneric

microorganisms supplied by a company.

In most cases, a TERA would be

required.

In several cases where researchers

contacted EPA regarding the status of

their field tests, EPA found that field

tests using intergeneric microorganisms

were not subject to TSCA, because the

field tests were being funded by other

Federal agencies and the researchers did

not foresee future commercial uses for

their microorganisms. Finding that these

field tests did not constitute commercial

R&D under TSCA, EPA directed the

researchers to the Federal agencies

which were the primary funding sources

for the field tests and suggested that

researchers should, at a minimum,

obtain reviews from these agencies

under relevant authorities, including

meeting the National Environmental

Policy Act (NEPA) responsibilities of

these other agencies.

Although EPA has chosen in this final

rule to follow an approach for

‘‘commercial purposes’’ similar to its

approach for traditional chemicals, EPA

recognizes that there are no differences

in risk depending on funding source.

EPA takes seriously its responsibilities

to address risk and intends to pursue

approaches laid out in the Coordinated

Framework for Regulation of

Biotechnology (51 FR 23302, June 26,

1986) to ensure an adequate network of

oversight of R&D activities. To this end,

EPA will work closely with other

agencies, particularly NIH.

3. Microorganisms eligible for the

R&D small quantities exemption. TSCA

section 5(h)(3) exempts from section 5

screening, chemical substances

manufactured or processed in small

quantities solely for R&D and directs

EPA to define small quantities by rule.

EPA’s regulations for traditional

chemicals at § 720.3(cc) define ‘‘small

quantities solely for R&D’’ as those

quantities that are ‘‘not greater than

reasonably necessary for ...[R&D]

purposes.’’ This definition of small

quantities for R&D has been appropriate

for traditional chemical substances,

because these chemicals do not have the

ability to increase their own volume or

amount. However, living

microorganisms may reproduce and

increase beyond the number initially

introduced, may establish in the

environment, and may spread beyond

the test site. Once they are released into

the environment or are no longer

contained, there is no longer an

assurance they will remain ‘‘small

quantities.’’

Therefore, EPA’s definition at § 725.3

of ‘‘small quantities’’ for

microorganisms is restricted to

microorganisms used under conditions

that meet the requirements of § 725.234,

which are designed to reduce the

probability of establishment by reducing

the number and frequency of viable

microorganisms emitted from a facility.

The small quantities exemption for

microorganisms is also referred to as the

‘‘contained structures’’ exemption,

because § 725.234(c) limits the

exemption to R&D activities in

contained structures.

Most of the comments EPA received

on its application of the section 5(h)(3)

exemption to R&D activities with

microorganisms in contained structures

requested clarification with regard to

the use of research microorganisms in

commerce, the use of genetic libraries,

and coordination with the NIH

Guidelines. None of the commenters

provided EPA with new information
17924 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

that would cause EPA to reconsider or

change the basis for its decision to

restrict the section 5(h)(3) exemption to

microorganisms used under conditions

meeting the requirements of § 725.234.

Consequently EPA has adopted the

proposed regulatory text for this

exemption with some revisions. The

requirements for this exemption are

found in the regulatory text in

§§ 725.232, 725.234 and 725.235. These

issues are discussed in the proposed

rule (59 FR 45539-42) and in the

Response to Comments document in

Unit IV.C.

For purposes of clarification, EPA has

modified requirements originally

included in proposed § 725.235. Most of

the proposed language was adapted,

with little revision, from the small

quantities exemption for traditional

chemicals at § 720.36. Upon further

reflection, EPA has determined that

some of that language is not appropriate

for microorganisms. Therefore, EPA has

deleted proposed § 725.235(a)(2), which

provided an exemption from the small

quantities notification requirements for

R&D in a laboratory, and proposed

§ 725.235(e), which related to impurities

and articles. Additionally, the

requirements at proposed § 725.235(c),

(d), and (f) have been moved to

§ 725.205(d), (e), and (f), respectively, as

these requirements apply to all R&D

activities under subpart E. EPA has

further revised § 725.205(f) to

specifically exclude microbial

pesticides by referring to the microbial

pesticide notification requirements that

were promulgated in September 1994

(59 FR 45612).

EPA disagrees with the commenter

who stated that EPA had not justified

the ‘‘wholesale removal of the R&D

exemption provided by Congress.’’

TSCA section 5(h)(3) does not provide

a complete exemption for all R&D, nor

has EPA removed the statutory

exemption wholesale. Rather, TSCA

section 5(h)(3) exempts from section 5

reporting chemical substances

manufactured or processed in small

quantities for R&D and specifically

directs EPA to define ‘‘small quantities’’

by rule. EPA has determined that the

definition of ‘‘small quantities’’ applied

at § 720.3 to traditional chemical

substances cannot be applied to all R&D

activities involving microorganisms for

the reasons discussed in the proposed

rule (59 FR 45539-40).

4. R&D subject to TSCA and another

Federal agency. In the proposed rule,

EPA discussed situations where R&D

activities might be subject to both TSCA

and another Federal authority. EPA

suggested different approaches to

dealing with overlapping jurisdiction,

depending on whether the R&D

activities were conducted in a contained

structure or involved intentional

environmental testing.

EPA proposed a complete exemption

from EPA-specific reporting under

TSCA section 5(h)(4) for research on

new microorganisms in contained

structures, if the research is regulated or

funded by a Federal agency which has

agreed to abide by the NIH Guidelines.

In the proposed rule (59 FR 45542-

43), EPA discussed exempting from

TSCA section 5 requirements the

intentional environmental testing of

new microorganisms, when another

Federal agency has clear regulatory

authority and EPA determines that the

other Federal agency’s review addresses

criteria equivalent to those which would

be evaluated under TSCA section 5.

Specifically, EPA indicated that it was

working with USDA/APHIS to develop

an exemption from TSCA section 5

requirements for R&D field tests

reviewed by APHIS under the Federal

Plant Pest Act and the Plant Quarantine

Act.

Several commenters supported the

proposal to exempt from EPA

requirements those researchers who

mandatorily comply with the NIH

Guidelines. Some commenters stated

that researchers who voluntarily comply

with the NIH Guidelines should also be

exempt from the TSCA section 5(h)(3)

requirements. Some commenters

specifically supported EPA’s discussion

of potentially deferring to other

agencies’ reviews and determinations,

when appropriate, for intentional

environmental testing of new

microorganisms. It was requested that

EPA clarify its relationship with USDA/

APHIS. Some commenters suggested

extension of EPA’s proposal to defer to

other Federal agencies.

EPA has retained at § 725.232(b) its

complete exemption from TSCA section

5 obligations for research on new

microorganisms in contained structures,

if the researcher is receiving funds from

another Federal agency which requires

compliance with the NIH Guidelines.

This includes all research, whether

directly funded by an agency or not, at

a university or institution that adheres

to the NIH Guidelines on an institutionwide basis as a condition of receiving

Federal funds. EPA developed this

exemption to avoid duplicative

oversight with other Federal authorities.

Researchers who are complying with the

NIH Guidelines voluntarily or through

vehicles such as contracts or local

regulations, will not be eligible for the

exemption at § 725.232, because their

research is not being overseen by

another Federal agency. However, as

discussed further below, EPA believes

that anyone who is complying with the

NIH Guidelines should be able to meet

the requirements of §§ 725.234 and

725.235 with little difficulty.

EPA agrees in principle with

commenters who believe that, when

consistent with the requirements of the

statutes involved, products subject to

another statute as well as to TSCA need

only be regulated by one of those

agencies. Presently, EPA has identified

the Plant Pest Act and Plant Quarantine

Act administered by USDA/APHIS as

presenting some degree of overlapping

jurisdiction with TSCA for

microorganisms. At this time EPA and

USDA do not know of any products

subject to overlapping jurisdiction.

Should such a situation arise, EPA will

work with APHIS to develop a proposed

exemption from TSCA section 5

requirements for R&D field tests subject

to overlapping jurisdiction. In the

future, should other cases of duplicative

oversight arise, EPA will work with the

other agencies involved to develop an

appropriate solution. These issues are

discussed in the Response to Comments

document in Unit IV.D.

5. Requirements for small quantities/

contained R&D exemption. EPA

indicated in the proposed rule (59 FR

45540) that for those researchers who

are voluntarily complying with, but are

not subject to, the NIH Guidelines, the

requirements of the R&D small

quantities exemption at § 725.234 could

be met by having the principal

investigator (PI) serve as the technically

qualified individual (TQI) required by

§ 725.234(b) and keep records indicating

that they abide by and are following the

NIH Guidelines for the specific TSCAsubject R&D activities. However, EPA

proposed to rely on the experience and

judgement of the TQI to select

containment and inactivation controls

appropriate to the microorganism(s)

being utilized. In some cases, the TQI

could find it appropriate to use NIH

Guidelines, and in others, the TQI might

not. EPA took this position, because

EPA recognized that many different

kinds of microorganisms displaying a

wide range of characteristics could

potentially be used in research and that

the type of controls appropriate for one

microorganism might have limited

relevance to other microorganisms. This

issue is discussed in the Response to

Comments document in Unit IV.E.

Several commenters indicated

support for use of the NIH Guidelines

and requested clarification and/or made

suggestions concerning the relationship

of the NIH Guidelines to the R&D small

quantities exemption. While EPA

considers the NIH Guidelines to provide
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17925

the primary standard for laboratory

research, EPA continues to believe that

it is appropriate to allow TQIs to have

the option of relying on their experience

and judgement in selecting appropriate

containment as opposed to being forced

to rely solely on the NIH Guidelines. In

addition, not all TSCA-subject

microorganisms will also be subject to

the NIH Guidelines, since the

Guidelines focus on research involving

recombinant DNA (rDNA) molecules

and EPA focuses on intergeneric

microorganisms as ‘‘new.’’ Therefore,

some researchers will need to rely for

some activities on EPA’s criteria at

§ 725.234, since their activities will not

be covered by the NIH Guidelines. In

structuring its approach, EPA believes it

has provided an appropriate measure of

flexibility to researchers. Additionally,

EPA believes that those researchers who

currently comply with the NIH

Guidelines, but are not eligible for the

exemption under § 725.232,

nevertheless can comply with the

requirements of §§ 725.234 and 725.235

with little additional burden beyond

that imposed by the NIH Guidelines.

With respect to the requirement at

§ 725.234(d)(2) for certification by an

authorized official, EPA recognized in

the proposal (59 FR 45540) that

Institutional Biosafety Committees

(IBCs) and similar committees are

charged with assessing the containment

selected by researchers. EPA encourages

the active use of such committees and

agrees that an authorized official may be

an IBC chair. EPA also evaluated the

comments on the burden imposed by

recordkeeping for the R&D small

quantities exemption. As EPA noted in

the proposal, EPA believes that persons

following the NIH Guidelines would

keep records as part of normal

procedures at an institution where IBCs

are responsible for ensuring the safety of

research. Such records are likely to be

adequate for meeting the provisions at

§ 725.234(d)(3). This issue is discussed

in more detail in the Response to

Comments document in Unit IV.E.,

which also provides a comparison of the

NIH Guidelines and the requirements of

§§ 725.234 and 725.235.

Several commenters suggested that

EPA adopt the NIH Guidelines as a

requirement for the R&D small

quantities exemption. As discussed

previously, EPA believes that it is more

appropriate to show researchers how the

use of the NIH Guidelines can fulfill the

requirements of the R&D small

quantities exemption and has included

a comparison discussion in the

Response to Comments document in

Unit IV.E.1. In general, EPA expects that

companies currently complying with

the NIH Guidelines will also be able to

satisfy the requirements of the R&D

small quantities exemption. Although

the NIH Guidelines do not explicitly

state that documentation of the

notification is required, the requirement

for such documentation can be readily

inferred in section IV. of the NIH

Guidelines. Because TSCA explicitly

requires such notification, researchers

may still need to verify that the

documentation maintained pursuant to

the NIH Guidelines includes

documentation of the notification as

specified in § 725.235(c)(1).

Like the NIH Guidelines, EPA’s

regulations cannot anticipate every

research situation. Therefore, using the

comparison of the NIH Guidelines and

the requirements of §§ 725.234 and

725.235 as guidance, researchers subject

to TSCA section 5 and complying with

the NIH Guidelines should evaluate

their specific research situation to

determine whether their use of the

Guidelines also fulfills the requirements

of §§ 725.234 and 725.235.

6. Exemptions from TERA reporting

for certain R&D activities conducted

outside a structure. In the proposed

rule, EPA discussed a process for

exempting small-scale field tests of

certain microorganisms from TERA

reporting. To qualify for the exemption,

certain criteria regarding the recipient

microorganisms, the source(s) and

characteristics of the introduced genetic

material, and the conditions of use

would need to be met. EPA proposed

certain strains of Bradyrhizobium

japonicum and Rhizobium meliloti as

candidates for exemption from TERA

reporting, based on EPA reviews of

voluntary PMNs for these

microorganisms submitted under the

1986 Policy Statement and field test

data generated in these field trials. In

response to comments, EPA has

modified some of the specific

conditions for the exemption. Some

commenters expressed concern about

EPA’s proposal to exempt strains

containing antibiotic resistance markers

from any source. EPA has determined

that for the exemption described at

§ 725.239, it will follow the conservative

course of only allowing use in B.

japonicum and R. meliloti of those

markers EPA has reviewed for use in

these microorganisms. This approach

would ensure that the probability of

presenting unreasonable risk would be

low for each antibiotic resistance

marker. The regulatory text at

§§ 725.239(a)(2)(ii)(A)(1) and

725.239(b)(2)(ii)(A)(1) has been

modified to limit structural genes

encoding marker sequences to those

encoding resistance to the aadH gene,

which confers resistance to

streptomycin and spectinomycin, in

these microorganisms. Based on EPA’s

analysis of use of this marker in

rhizobia, and including consideration of

the advice of the January 4, 1995 BSAC

Subcommittee, the use of streptomycin

and/or spectinomycin resistance

markers in B. japonicum and R. meliloti

currently meets this requirement of the

exemption.

EPA recognizes that the exemption at

§ 725.239 is narrow and may only apply

to very few research projects. It may be

the case in the early years of the TERA

program that TERA exemptions are

narrowly written to apply to specific

microorganisms that have completed

TERA review. However, EPA hopes that

in the longer term as EPA gains greater

experience reviewing intergeneric

microorganisms for environmental uses,

broader exemptions can be written. To

that end, EPA has placed general

requirements for the TERA exemption

in § 725.238 and will use § 725.239 to

list certain microorganisms for the

exemption and the specific conditions

of use as needed.

7. TERA reporting process. Under

section 5(h)(4), EPA proposed to

conditionally exempt from MCAN

notification certain R&D activities

involving new microorganisms. The

exemption is conditional, since

researchers must submit a TERA, an

abbreviated notification. Due to the

availability of other exemptions for R&D

activities discussed in this preamble,

EPA expects that the TERA will be used

primarily for environmental research. In

the proposed rule (59 FR 45535), EPA

indicated that its goal was to review

TERAs in 60 days, but that for good

cause, EPA could extend the initial

TERA review period by an additional 60

days, for a total of 120 days. This

condition, the information requirements

for submitters, and the TERA approval

process have not been changed from the

proposed rule. This exemption is

discussed in the proposed rule (59 FR

45535-36, 45543-44) and in the

Response to Comments document in

Unit IV.G.

EPA received some comments

supporting the TERA process. Other

commenters who opposed the use of the

TERA process and stated that some of

the information requirements were too

extensive, also stated that specific

monitoring data should be required.

EPA has made minor revisions to the

TERA requirements at §§ 725.250

through 725.288. Issues raised about

state coordination are discussed in the

next section.

EPA believes that it is necessary to

establish a review and approval process
17926 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

specifically for R&D activities involving

environmental release. While many

field tests of new microorganisms will

be determined to pose low risks, this

assumption cannot be made for field

tests in general, and thus EPA finds

some type of review is warranted.

However, EPA recognizes that full

MCAN reporting also may not be

warranted. Therefore, EPA has chosen

to develop a review and approval

process specifically tailored to address

R&D.

EPA believes that the information

requirements proposed for the TERA are

appropriate. EPA must have sufficient

information to evaluate the health and

environmental effects of a planned field

test. However, because a variety of

microorganisms are potentially subject

to TSCA, the requirements indicated in

§ 725.255 are necessarily broad. Not all

of the requirements are equally

applicable to all microorganisms.

Submitters are encouraged to consult

with EPA prior to preparing TERAs, so

that appropriate information needs and

concerns may be identified.

EPA has made minor changes to the

regulatory text at § 725.270 to clarify

that EPA is approving or denying the

TERA. Therefore, the term ‘‘TERA

agreement’’ which was used in the

proposed rule has been changed to

‘‘TERA approval.’’ In addition to

approving or denying the TERA, EPA

may provide, in the TERA approval,

conditions under which the R&D

activity described in the TERA must be

conducted in order for EPA to make the

TSCA section 5(h)(4) finding that the

R&D activity will not present an

unreasonable risk to health or the

environment. During the TERA review

period, EPA may identify issues that

need further information before EPA can

give its approval for the R&D activity to

proceed. EPA or the submitter may

suspend the review period, if necessary.

When EPA approves a TERA, the

submitter must conduct the R&D

activity only as described in the TERA,

and any amendments to the TERA, and

under any conditions specified by EPA

in its approval of the TERA.

8. Options for oversight of R&D

activities. As discussed above, EPA

proposed an approach for oversight of

R&D activities which included a variety

of exemptions from the full 90-day

reporting process required for general

commercial use activities. EPA’s goal

was to provide a flexible process which

tailored oversight to the level of risk.

EPA asked for comment on its R&D

exemptions, all of which have been

discussed above, and indicated that the

public could suggest other options for

consideration. Options for oversight

suggested by the commenters are

discussed in the Response to Comments

document in Unit IV.H. For a variety of

reasons, EPA concluded that the

alternatives suggested would not

adequately permit EPA to fulfill its

statutory duties under TSCA section 5.

Some commenters, while indicating

that the R&D exemptions were

comprehensible, did not believe that

level of oversight correlated to level of

risk. EPA disagrees with comments that

the level of oversight imposed in its

R&D exemptions is not correlated to

level of risk. EPA discusses its view of

the relationship between risk and the

TSCA definition of ‘‘new

microorganism’’ in Unit II.D. of the

Response to Comments document. EPA

has chosen to implement its R&D

oversight in a manner which

distinguishes between R&D activities in

contained structures and R&D activities

involving intentional release to the

environment because of the greater

overall potential in the latter case for

survival, dissemination, and exposure to

the microorganisms. Within this broad

structure, EPA has developed several

exemptions which recognize the

differing risk potentials presented by

different settings and organisms. These

exemptions have been discussed above

and are discussed in greater detail in

Units IV.C. through G. of the Response

to Comments document.

In the proposed rule (59 FR 45536-

37), EPA briefly discussed an alternative

exemption for certain R&D releases.

This alternative would contain

requirements for documentation and

recordkeeping by a TQI and certification

by an authorized official. EPA is not

finalizing this option at this time.

However, EPA plans to propose an

exemption along these lines at a later

date to allow the public an opportunity

to comment on the new information on

which EPA is relying to support the

exemption.

D. Other Issues

1. Microorganism definition. In the

proposed rule (59 FR 45550-51), EPA

defined ‘‘microorganisms’’ in § 725.3 as

those organisms classified under the 5-

kingdom system of Whittacker (Ref. 5)

in the kingdoms Monera (or

Procaryotae), Protista, and Fungi, the

Chlorophyta and the Rhodophyta of the

Plantae, and viruses and virus-like

particles. Therefore, this definition

includes, but is not limited to, bacteria,

protozoa, fungi, mycoplasmas,

mycoplasma-like organisms,

spiroplasmas, microphytoplanktons,

green and red algae, viruses, and viruslike particles (e.g., viroids, satellites,

and virusoids). Should new categories

of organisms within the Monera,

Protista, Fungi and the Chlorophyta and

Rhodophyta of the Plantae be identified,

these would also be considered

microorganisms under this definition.

EPA proposed to treat viruses of other

microorganisms (also termed phages) as

MGEs. EPA’s MGE policy is discussed

in the proposed rule (59 FR 45528) and

in Unit II.D. of the Response to

Comments document. In the proposed

rule, EPA indicated that it was not able

to identify uses of viruses of

macroorganisms that might be subject to

TSCA. EPA asked if it was appropriate

to apply the intergeneric interpretation

to viruses of macroorganisms if TSCA

uses for such viruses were identified.

Commenters thought the proposed

definition of ‘‘microorganism’’ was

reasonable and included the appropriate

organisms. Thus, EPA will retain the

definition of ‘‘microorganism’’ as

discussed in the proposed rule and

found in the regulatory text in § 725.3.

EPA has modified the definition to

clearly indicate in the regulatory text

that EPA is using the 5-kingdom

classification of Whittacker.

Additionally, as discussed in the

proposal, EPA will treat phages as

MGEs. No commenters identified

current or imminent TSCA uses of

viruses of macroorganisms. Therefore,

EPA believes the best use of limited

resources would be to develop an

approach under TSCA for viruses of

macroorganisms in the future if TSCA

uses are identified. The definition of

microorganism is discussed in the

Response to Comments document in

Unit V.A.

2. TSCA Inventory. EPA described in

the proposed rule (59 FR 45551-52) how

it planned to explicitly list

microorganisms on the TSCA Inventory

and the rationale for the proposed

listing. EPA proposed to identify

microorganisms on the Inventory using

a taxonomic designation and a

consistent set of supplemental

information on phenotypic and

genotypic traits necessary to identify the

microorganism as precisely as possible.

Additionally, EPA indicated that it was

considering requiring that

microorganisms listed on the Inventory

be deposited in a recognized culture

collection.

In the proposed rule, EPA advised

manufacturers and importers of any of

the 192 microorganisms reported in

1978 for the initial TSCA Inventory that

EPA planned to remove from the

Inventory the explicit listing of these

microorganisms. EPA believed that most

of these microorganisms are not

intergeneric; therefore they would be

automatically included on the Inventory
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17927

and do not need to be explicitly listed.

EPA asked manufacturers and importers

of these microorganisms to inform EPA

if any of the microorganisms were

intergeneric and should not be removed

from the Inventory.

In response to EPA’s request for

comments on developing a requirement

for culture collection deposit, several

commenters strongly opposed the

development of any requirement for

deposit of a microorganism in a culture

collection. One commenter was

concerned about the effect that an EPA

requirement would have on patent

protection. Others believed that such a

requirement would be unnecessary and

onerous at the R&D stage. EPA has

considered the concerns raised by

commenters who oppose the culture

collection requirement and has decided

that deposit of new microorganisms in

recognized culture collections is not

necessary. Therefore, EPA has not made

this a requirement for microorganisms

subject to TSCA section 5 reporting.

Commenters asked that EPA clarify

the type of taxonomic designation to be

used for Inventory listing and indicate

how revisions to taxonomy would be

accommodated on the Inventory. Others

asked EPA to clarify what is ‘‘new’’

under TSCA, particularly with respect

to minor changes made during strain

improvement of microorganisms already

listed on the Inventory. EPA agrees that

Inventory listing for intergeneric

microorganisms is more complex than

listing for most traditional chemicals.

As indicated above, EPA plans to

consider modifications and

clarifications to its intergeneric

interpretation in the future. Future

modifications to the intergeneric

interpretation will also affect how

microorganisms are listed on the

Inventory. A subcommittee of EPA’s

BSAC, which met on July 22, 1991,

when questioned on EPA’s proposed

approach to Inventory listing for

microorganisms, suggested that EPA

continue on a case-by-case basis and

gain additional experience before

finalizing its requirements for Inventory

listing. Therefore, EPA believes it

prudent to defer a fuller development of

Inventory listing for microorganisms

until it has considered modifications to

the intergeneric interpretation and gains

additional experience. Meanwhile, EPA

will use a case-by-case approach to

Inventory listing for new

microorganisms. Inventory issues are

discussed in the Response to Comments

document in Unit V.B. EPA has

provided some clarification regarding

use of taxonomy in the Response to

Comments document in Unit II.D.

Additional guidance on Inventory

listing may also be found in the

proposed rule preamble (59 FR 45551-

52).

Commenters requested that EPA

provide a ‘‘grandfather’’ period by

opening up the Inventory for 1 year after

the final rule is published to allow

products currently in commerce to be

listed. One commenter requested that

intergeneric products currently in

commerce be automatically placed on

the Inventory. EPA disagrees with the

commenters who believe that a

‘‘grandfather’’ period is necessary. Since

the publication of the 1986 Policy

Statement in June 1986, EPA has

required PMN reporting for general

commercial use of intergeneric

microorganisms subject to TSCA.

Although different scopes of oversight

have been discussed in the intervening

years, the Policy Statement has

remained in effect all that time.

Therefore, EPA believes that the public

has had sufficient notice of its program

and that intergeneric microorganisms

currently in commerce and being used

for TSCA purposes should already have

been reported to EPA.

In response to the EPA proposal to

delist 192 microorganisms currently

listed on the Inventory by genus and

species only, commenters discussed

their concerns. One commenter stated

that there was no information about the

phenotypic characteristics of these

strains or about any introduced DNA.

EPA wishes to clarify its position on

microorganisms currently listed on the

Inventory. These microorganisms can be

divided into two groups: (1) Those

reported to the initial Inventory in the

late 1970s, and (2) those listed after

EPA’s review of PMNs and receipt of

Notices of Commencement to

manufacture. EPA has no concerns

about the Inventory status of the second

group, because these microorganisms

were all reported to EPA under the 1986

Policy Statement and therefore are

intergeneric and are appropriately

explicitly listed. The listings for these

microorganisms include descriptive

information to specifically identify them

beyond the genus and species

designations.

Such is not the case for the first

group, the 192 microorganisms reported

for the initial Inventory in the late

1970s. As one commenter noted, these

microorganisms are primarily listed by

genus and species. EPA believes that

most of these microorganisms are

naturally occurring or have been

modified by methods that do not

involve the introduction of DNA from

an organism in another genus and thus

in many cases would not need to be

explicitly listed. To confirm this

assumption, EPA requested comment

from persons manufacturing or

importing any of the 192

microorganisms. No comments were

received on the status of these

microorganisms. EPA wishes to ensure

that all microorganisms which are

explicitly listed on the Inventory are

intergeneric and are described in a

consistent manner. Therefore, EPA has

concluded that the 192 microorganisms

are not intergeneric and, thus, are

automatically on the Inventory under

§ 725.8(b). EPA will remove the explicit

listings from the Inventory in a separate

action under the authority of TSCA

section 8(b).

3. Confidential Business Information.

EPA proposed to require upfront

substantiation of confidential business

information (CBI) claims in all

submissions for general commercial

uses of microorganisms. Under the

proposal, anyone submitting a MCAN, a

Test Marketing Exemption (TME), Tier I

certification, or a Tier II exemption

request would be required to

substantiate CBI claims at the time of

submission. With respect to upfront

substantiation for TERAs, EPA proposed

two options and asked for public

comments on both. Option 1 would

have required upfront substantiation of

all CBI claims in TERAs. Option 2

would not have required upfront

substantiation of CBI claims in TERAs,

but would only require CBI

substantiation after EPA received a

Freedom of Information (FOIA) request.

One commenter asked for additional

clarification of EPA’s CBI policy for

microorganism submissions. Two

commenters supported EPA’s proposal

to require upfront substantiation of CBI

claims for submissions for both research

and general commercial use. However,

most commenters opposed upfront

substantiation of CBI claims in R&D

submissions, indicating that the

requirement was too burdensome for

R&D, especially because it was

important to have proprietary protection

for R&D activities. Some commenters

specifically opposed upfront

substantiation of CBI claims in

submissions for R&D submissions only.

Others opposed upfront substantiation

of CBI claims in any microorganism

submission, arguing that EPA’s

approach to substantiation of CBI claims

in microorganism submissions should

not differ from EPA’s approach to

substantiation of CBI claims in

traditional chemical submissions.

Considering the competing interests

in the comments received and the

burden imposed on industry, EPA has

decided not to require upfront

substantiation of CBI claims in TERAs
17928 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

but will retain the upfront

substantiation requirement for CBI

claims in MCANs, TMEs, Tier I

certifications, and Tier II exemption

requests. In the past several years,

submitters of voluntary PMNs for field

tests of new microorganisms have

claimed very little, if any, CBI.

However, if, in the future, EPA finds

that CBI claims have increased in

TERAs and that insufficient information

is available to the public during the

shorter TERA review period, EPA may

find it necessary to reconsider the

decision not to require upfront

substantiation of CBI claims in TERAs.

At this time, EPA has revised the

regulatory text at § 725.94(a)(2) to delete

the requirement for upfront CBI

substantiation. In the case of general

commercial use submissions, EPA

believes that the upfront substantiation

requirement for CBI claims will impose

little burden on submitters of MCANs,

TMEs, Tier I certifications, and Tier II

exemption requests. Because persons

preparing these submissions are ready

to put their products on the market, they

will have a greater understanding of the

products and any CBI issues and,

therefore, should be able to justify why

it will continue to be necessary to keep

certain information confidential. In

addition, given the shorter review

period for TMEs and Tier II exemption

requests, sufficient information may not

be made available to the public if

upfront substantiation of CBI claims is

not required. In particular, EPA may not

be able to comply with all deadlines if

a FOIA request is received.

4. Antibiotic resistance markers. EPA

did not establish a general policy for

addressing antibiotic resistance markers

as part of its proposed rule. Use of

antibiotic resistance markers was only

discussed as part of the exemption from

TERA reporting proposed for certain

modified strains of Bradyrhizobium

japonicum and Rhizobium meliloti at

proposed § 725.239. Although EPA only

discussed the use of antibiotic

resistance markers as part of its proposal

for exempting two specific

microorganisms from TERA reporting,

EPA also received comments addressing

more generally the use of antibiotic

resistance markers. As discussed above,

EPA has responded to comments on the

TERA exemption, including revising the

regulatory text at § 725.239 regarding

use of antibiotic resistance markers in

those microorganisms. The general

discussion of antibiotic resistance

markers can be found in the Response

to Comments document in Unit V.E.

EPA recognizes that many factors

affect the health and safety evaluation of

use of antibiotic resistance markers. The

use of antibiotic resistance markers is a

complicated issue which has

ramifications for products beyond the

scope of TSCA. Because of the

complexity, EPA will not issue a general

policy on the use of antibiotic resistance

markers, but will continue to evaluate

their use in specific microorganisms on

a case-by-case basis as submissions are

received. EPA plans to pursue this issue

in consultation with other Federal

agencies who have an interest in this

issue.

5. State coordination. The proposed

rule discussed EPA’s procedures under

the 1986 Policy Statement for

coordinating reviews and sharing

scientific information with appropriate

State and local authorities (59 FR

45531). EPA proposed to require

persons preparing TERA submissions

for R&D activities involving release to

the environment to provide evidence of

having notified appropriate State

authorities. This issue is discussed in

the Response to Comments document in

Unit V.F.

Although one commenter supported

EPA’s proposed requirement for State

coordination, several commenters

opposed the requirement. EPA has

developed comprehensive procedures to

coordinate reviews of submissions and

to share scientific information with

appropriate State and local authorities

to the fullest extent possible without

violating TSCA CBI requirements.

Comments and concerns raised by the

State(s) are given careful attention

during the review process. State

personnel receive a copy of any

document which addresses the

conditions under which the R&D

activity, generally a field test, can be

performed.

EPA’s coordination procedures would

make researcher notification redundant.

Consequently, EPA has revised

§§ 725.238(b)(3)(ii) and 725.255(e)(1)(vi)

to remove the requirement that

submitters include evidence that State

authorities have been notified in the

TERA exemption certification and

TERA submission, respectively. EPA

will continue to encourage submitters to

advise State and local authorities of

their field test plans, although this will

not be a requirement. In cases where

submitters have informed State and

local authorities of their test plans, EPA

believes that it is appropriate to require

that submitters inform EPA of this

notification as part of their submissions.

VI. Economic Analysis

A. Introduction

EPA has prepared a Regulatory Impact

Analysis (RIA) assessing the costs,

benefits, and associated impacts of

regulating new microorganisms under

TSCA as set forth in this final rule. A

summary of key findings and estimates

is presented below.

B. Regulated Community

Although unable to quantify the exact

magnitude of activity in biotechnology

sectors affected by this rulemaking, the

Agency believes that activities involving

microorganisms falling within the scope

of the final rule comprise a modest

share of overall activity. EPA estimates

that approximately 130 firms may be

involved in commercial R&D or in

general commercial use of potentially

regulated microorganisms. In terms of

revenue, the potentially affected

universe appears to be divided sharply

between large and small firms. EPA

estimates roughly one-half of the

companies potentially affected to have

annual sales of $40 million or more,

while most of those remaining are

estimated to have sales under $10

million. For many of these firms,

however, revenue generated from

activities subject to this rule is believed

to represent only a small portion of

reported sales. At proposal, EPA also

estimated that approximately 300

universities could be affected by the

rulemaking. However, in the final rule,

because of its implementation of a

definition of commercial purposes at

R&D based on financial indicia, EPA

believes substantially fewer universities

will be affected.

C. Costs to Submitters

Due to data limitations and the

uncertainties associated with projecting

future product development activities in

biotechnology application areas subject

to the final rule, EPA’s estimates of the

costs of compliance associated with this

rulemaking action have been only

partially quantified. In cases where the

Agency was able to generate quantified

estimates of compliance costs,

information which would have

permitted the development of more

accurate estimates was frequently

unavailable; in such cases, the best

available information was used, and the

estimates are believed to represent a

reasonable approximation of actual

costs attributable to the rule. A

summary of EPA’s quantitative cost

estimates follows.

In assessing the potential cost impact

of the final rule, EPA focussed on two

impact years, ‘‘Year 1’’ and ‘‘Year 5.’’

Year 1 costs are based on the expected

costs associated with biotechnology

products in the early stage of regulation,

while year 5 costs are based on a

projection of conditions following some
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17929

industry growth, subsequent to rule

promulgation. This approach was used

because of the relative immaturity of the

biotechnology sectors potentially

subject to the rule, and the difficulty in

attempting to forecast long-term

technological and marketing

developments. It is emphasized,

however, that estimated costs could be

significantly higher in the long-term,

owing to continued industry expansion.

Four major cost areas were identified,

based on an analysis of the requirements

of the rule. These areas were: costs

incurred in preparing various types of

notification submissions or

documentation; costs incurred in

complying with any post review

requirements for monitoring or controls

that may be imposed by EPA as a result

of risk concerns and uncertainties; costs

incurred in substantiating CBI claims;

and one-time costs attributable to rule

familiarization.

Incremental costs to industry

(industry-wide costs net requirements

under current policy), estimated based

on prevailing wage rates for 1987, were

estimated to fall between $890,000 to

$2.2 million in year 1 and between

$70,000 to $510,000 in year 5. (Year 5

costs account for rule familiarization

only in the case of new firms entering

the affected market areas, and therefore

are much less than year 1 costs, where

rule familiarization costs were summed

over all affected entities.) Adjusted to

reflect current rates (1995 dollars),

estimated incremental costs range from

$1.2 million to $3.0 million in year 1

and from $95,000 to $690,000 in year 5.

Cost impacts on individual products

will vary, depending on application

area. Submitters qualifying for full or

partial exemptions in connection with

microorganisms intended for general

commercial use will realize net savings

relative to current reporting

requirements, while submitters filing in

connection with field experiments may

realize an increase in regulatory burden

under the rule.

D. Costs to the Federal Government

EPA estimated the potential costs to

government associated with the final

rule. These costs arise in connection

with the Agency’s processing of

individual notification submissions.

In estimating government cost

impacts, EPA included costs estimated

to be incurred in reviewing each

submittal. EPA professionals and

members of the Biotechnology Science

Advisory Committee were assumed to

be involved in such review. In the event

that post-review restrictions are placed

on a specific activity, such as

monitoring during a field test,

additional costs attributable to the

drawing up of regulatory documentation

would be incurred.

Incremental costs to the government

were estimated, using 1987 as the base

year for valuing compensation, to fall

between $115,000 to $122,000 in year 1,

while year 5 costs were estimated to fall

between -$105,000 (a net savings) to

$4,000. Using 1995 as base year for

compensation, estimated incremental

costs range from $156,000 to $165,000

in year 1 and from -$143,000 to $5,300

in year 5. Savings arise in connection

with the substantial number of full

reviews that will be avoided due to the

exemption provisions of the rule.

E. Benefits of the Rule

EPA’s regulation of new

microorganisms under TSCA provides

benefits to society through reduction of

the potential for adverse impacts on

health and the environment resulting

from the use of such organisms. This

benefit is achieved by screening new

microorganisms and, when appropriate,

imposing controls on microorganism

use to protect society from costly and

possibly irreversible damages.

For microorganisms in general

commercial use, risk reduction

attributable strictly to the notification

requirements of the final rule would be

marginal, as these requirements are

based on current policy. However, the

rule enhances and contributes to the

overall risk reduction potential of the

Agency’s program under TSCA by

providing for a more efficient regulatory

strategy relative to current policy,

focussing society’s resources on those

new microorganisms of greatest

concern.

For microorganisms in commercial

R&D, a greater proportion of overall risk

reduction can be attributed to the rule,

since reporting in connection with field

experiments has been voluntary since

1986. Though the Agency has received

voluntary submittals, it is uncertain

whether this practice is universal, or

whether those filing voluntarily would

continue to do so in the absence of these

rules.

Over the long-term, regulation is also

likely to encourage development of

additional information concerning fate

and effects of new microorganisms, to

encourage the development of

microorganisms which pose low

concern for effects on human health and

the environment, and to encourage

public input into decisions concerning

the use of new microorganisms.

Benefits may also be realized through

the rule’s potential impact on the pace

of product development. A less

uncertain regulatory climate could

stimulate business activity, as could a

more reassured public. The rule may

also reduce the possibility of continued

regulatory activity at the State and local

level. A national system of potentially

uncoordinated rulemaking initiatives

could lead to market distortion and

hamper competitiveness.

F. Effects of the Rule on Innovative

Activity

As a result of this final rule, members

of the regulated community may find

product development strategies in

connection with certain products to

require reassessment. Since impacts of

this nature could influence the degree of

emphasis a firm places on innovative

activity, the potential for innovation

impacts was investigated.

Though great uncertainty regarding

regulatory costs and the potential for a

particular product’s commercial success

make it impossible to estimate

innovation impacts quantitatively, the

effects of added regulatory costs and

delays on a product’s lifetime cash-flow

was examined. More specifically, a

number of plausible product

development scenarios were modeled

incorporating assumptions regarding

expenditures and returns over the

course of a product’s useful life (from

research to obsolescence). Regulatory

burdens were then factored into the

models, and profit impacts observed.

Impacts realized when total regulatory

costs were assumed to reach the upperbound of EPA’s estimated range could

result in severe profit reductions in

some cases; however, in general, EPA’s

analysis indicated that impacts should

not be prohibitive, particularly when

incremental costs are considered.

Factors such as length of delay related

to regulatory review, return rate, and

obsolescence rate all play important

roles in determining the impact of EPA’s

program on innovative activity, and

these factors are expected to be highly

variable and product-specific.

G. Impacts on Small Business

EPA survey data suggest 42 percent of

companies potentially affected by the

rule may be small businesses. Though

data were not available allowing the

Agency to employ standard criteria for

assessing the magnitude of small

business impacts, the finding of a

substantial portion of the regulated

community to be small businesses

prompted EPA to propose options to

provide relief to such businesses. The

options considered included reducing

CBI substantiation requirements and the

elimination of the $100 filing fee.

Comments were submitted indicating

concern for the rules impacts on
17930 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

products of low-value or limited use,

and for cost impacts on small

companies. Comments were also

received on the Agency’s proposed

alternatives for substantiation of CBI

claims in connection with TERA

submissions.

With regard to comments regarding

smaller-scale product development and

cost impacts on small business, EPA

finds that, because smaller scale projects

would most likely be exempt or involve

a relatively limited set of use and

exposure scenarios, burdens due to

regulatory review would be expected to

be minimal; thus, the impacts of greatest

concern to smaller institutions or

organizations could be frequently

mitigated. In considering comments

regarding CBI substantiation, EPA has

decided not to require upfront CBI

substantiation in connection with TERA

submissions, as most commenters

generally indicated upfront

substantiation to be overly burdensome

for R&D. Since the Agency considered

reducing up-front CBI substantiation

requirements for small businesses

submitting TERAs in its IRFA, EPA

views the CBI substantiation

requirements contained in the final rule

as providing important burden relief to

small businesses (or any business)

conducting R&D.

VII. Public Record

EPA has established a public record

for this rulemaking (docket control

number OPPTS–00049C). The record

includes all information considered by

EPA in developing this final rule. This

includes all information in the docket,

as well as information referenced in

documents in the docket. A public

version of the record without any

confidential information is available in

the TSCA Public Docket Office from

noon to 4 p.m., Monday through Friday,

except legal holidays. The TSCA Public

Docket Office is located in Rm. NEG607, Northeast Mall, 401 M St., SW.,

Washington, DC.

EPA has also made this final rule and

certain support documents available

electronically. They may be accessed

through the Internet at: gopher.epa.gov

or the Office of Pollution Prevention

and Toxics Biotechnology home page at

http://www.epa.gov/opptintr/biotech/.

The record now includes the

following items:

1. All prior Federal Register Notices,

and supporting public dockets, relating

to the regulation of microbial products

of biotechnology under TSCA. These

include:

a. The 1984 Proposed Policy

Statement (49 FR 50856, December 31,

1984).

b. The 1986 Policy Statement (51 FR

23302, June 26, 1986).

c. ‘‘Biotechnology; Request for

Comment on Regulatory Approach,’’ 54

FR 7027, February 15, 1989).

2. Public comments submitted in

response to each of the above Notices,

including the comments received at the

September 1989 Meeting which was

held to discuss TSCA regulatory options

for oversight of R&D.

3. ‘‘Principles for Federal Oversight of

Biotechnology: Planned Introduction

Into the Environment of Organisms

With Modified Hereditary Traits,’’

Office of Science and Technology

Policy, 55 FR 31118, July 31, 1990.

4. Reports of all BSAC meetings

pertaining to the development of this

final rule.

5. The Regulatory Impact Analysis for

this final rule.

6. Support documents and reports.

7. Records of all communications

between EPA personnel and persons

outside EPA pertaining to the

development of this final rule. (This

does not include any inter- or intraagency memoranda, unless specifically

noted in the Index of this docket.)

8. The docket also includes published

literature that is cited in this document.

9. The Response to Comments

document responding to the public

comments received on the September

1994 proposed rule, and all references

cited therein.

VIII. References

The following books, articles, and

reports were used in preparing this final

rule and were cited in this notice by the

number indicated below:

1. Priest, F. G., M. Goodfellow, L.A.

Shute, R.C.W. Berkeley. 1987. ‘‘Bacillus

amyloliquefaciens. sp. nov., nom.rev.’’

Internat. J. Syst. Bacteriol. 37:69-71.

2. U.S. Department of Health Human

Services, National Institutes of Health

(NIH). 1994. ‘‘Guidelines for Research

Involving Recombinant DNA Molecules

(NIH Guidelines)’’ (59 FR 34496, July 5,

1994).

3. OECD. 1988. ‘‘Recombinant DNA

Safety Considerations.’’ OECD, Paris.

4. Radian Corporation. 1996. ‘‘Review

of past premanufacture notices for

potential containment criteria for the

5(h)(4) exemptions in the proposed

biotechnology rule.’’ U.S.

Environmental Protection Agency,

Office of Pollution Prevention and

Toxics, Chemical Engineering Branch,

unpublished. Washington, D.C.

5. Atlas, R. and Bartha. R. 1987.

‘‘Microbial Ecology.’’ Chapter 2 ‘‘Survey

of Microorganisms,’’ pg. 19-60.

Benjamin/Cummings Publishing

Company, Inc. Menlo Park, CA.

6. Battelle. 1988. ‘‘Final Report on

Biosafety in Large-Scale rDNA

Processing Facilities.’’ 4 volume set.

U.S. EPA, Risk Reduction Engineering

Laboratory, Cincinnati, OH.

IX. Regulatory Assessment

Requirements

A. Executive Order 12866

Under Executive Order 12866 (58 FR

51735, October 4, 1993), it has been

determined that this rule is

‘‘significant’’ because it may raise novel

policy issues arising out of legal

mandates. As such, this action was

submitted to OMB for review, and any

comments or changes made in response

to OMB suggestions or

recommendations have been

documented in the public record.

B. Regulatory Flexibility Act

Pursuant to section 605(b) of the

Regulatory Flexibility Act (RFA) (5

U.S.C. 601 et seq), the Agency hereby

certifies that this final rule will not have

a significant adverse economic impact

on a substantial number of small

entities. The factual basis for this

determination is contained in the small

business regulatory flexibility analysis,

which is included as part of the RIA

accompanying this final rule, and is

summarized in Unit V. of this preamble.

In sum, EPA believes that the

mechanisms outlined in the final rule

will minimize economic impacts on

small businesses as much as possible,

and has determined that the rule should

not unduly burden small entities, nor

hinder the industry as a whole from

pursuing a full range of product

applications.

Information relating to this

determination has been included in the

docket for this rule, and will be

provided to the Chief Counsel for

Advocacy of the Small Business

Administration upon request.

C. Paperwork Reduction Act

The Office of Management and Budget

(OMB) has approved the information

collection requirements contained in

this rule under the provisions of the

Paperwork Reduction Act, 44 U.S.C.

3501 et seq. and has assigned OMB

control number 2070-0012 (EPA ICR No.

574).

This request is for an amendment to

an existing ICR covering EPA’s

Premanufacture Notice (PMN) review

program as is necessary to: (1) Collect

information on new microorganisms

manufactured or imported for

commercial use, and certain new

microorganisms used for research and

development (R&D); (2) reduce reporting
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17931

requirements for certain categories of

new microorganisms; and (3) require

recordkeeping demonstrating

compliance with conditions of certain

exemptions for new microorganisms.

Section 5 of TSCA gives EPA

authority to review chemical substances

prior to their manufacture, importation,

or processing in the U.S. in order to

determine whether such substances may

present an unreasonable risk of injury to

health or the environment. As explained

in the preamble to the proposed rule

and affirmed in Unit IV. earlier in this

preamble, the Agency has determined

such chemical substances to include

microorganisms. To make a reasoned

evaluation of the risk associated with

new microorganisms, EPA needs data

on each microorganism’s genetic makeup; physical, chemical, genetic or

phenotypic properties; manufacturing

process; worker exposure;

environmental release; production

volume; potential industrial,

commercial, and consumer use; and

related test data. The submission of

such data is mandatory, pursuant to

section 5(a)(1) of TSCA, 15 U.S.C. 2604,

and is to be submitted 90 days before

manufacture or import begins. The

confidentiality of collected information

will be maintained pursuant to the

provisions of TSCA, 15 U.S.C. 2613.

The projected annual incremental cost

to private parties associated with the

rule is $1.2 million, with an associated

burden of 41,000 hours. Annual

incremental costs may be broken down

into two components - initialization or

start-up costs (rule familiarization),

estimated to be $575,000, and costs for

information disclosure and maintenance

of records, estimated to be $600,000.

Annual burden is estimated to be

distributed among 218 responses,

averaging 188 hours per response. The

number of potential respondents is

estimated to be about 400 (not every

possible respondent is expected to file

each year).

Burden means the total time, effort, or

financial resources expended by persons

to generate, maintain, retain, or disclose

or provide information to or for a

Federal agency. This includes the time

needed to review instructions; develop,

acquire, install, and utilize technology

and systems for the purposes of

collecting, validating, and verifying

information, processing and

maintaining information, and disclosing

and providing information; adjust the

existing ways to comply with any

previously applicable instructions and

requirements; train personnel to be able

to respond to a collection of

information; search data sources;

complete and review the collection of

information; and transmit or otherwise

disclose the information.

An Agency may not conduct or

sponsor, and a person is not required to

respond to a collection of information

unless it displays a currently valid OMB

control number.

D. Unfunded Mandates Reform Act and

Executive Order 12875

Pursuant to Title II of the Unfunded

Mandates Reform Act of 1995 (UMRA)

(Pub. L. 104-4), EPA has determined

that this action does not contain a

Federal mandate that may result in

expenditures of $100 million or more

for State, local, and tribal governments,

in the aggregate, or the private sector in

any 1 year. The costs associated with

this action which are described in the

Executive Order 12866 section above are

well below $100 million for the private

sector. This rule does not impose any

duties upon States and local

government. Therefore, this action is not

subject to the requirements of sections

202 and 205 of the UMRA.

E. Executive Order 12898

Pursuant to Executive Order 12898

(59 FR 7629, February 16, 1994),

entitled Federal Actions to Address

Environmental Justice in Minority

Populations and Low-Income

Populations, the Agency has considered

environmental justice related issues

with regard to the potential impacts of

this action on the environmental and

health conditions in low-income and

minority communities. The Agency has

determined that nothing in these

notification procedures shall contribute

to disproportionately high and adverse

human health or environmental effects

on such communities. This final rule

describes informational requirements

prior to manufacture, process, or import

of new microorganisms based only on

such microorganisms’ genetic

characteristics and, as such, shall not

have the effect of excluding populations

from participation in, denying

populations the benefits of, or

subjecting populations to discrimination

because of their race, color, or national

origin.

F. Submission to Congress and the

General Accounting Office

Under 5 U.S.C. 801(a)(1)(A) of the

Administrative Procedure Act (APA) as

amended by the Small Business

Regulatory Enforcement Fairness Act of

1996 (Title II of Pub. L. 104-121, 110

Stat. 847), EPA submitted a report

containing this rule and other required

information to the U.S. Senate, the U.S.

House of Representatives and the

Comptroller General of the General

Accounting Office prior to publication

of the rule in today’s Federal Register.

This rule is not a ‘‘major rule’’ as

defined by 5 U.S.C. 804(2) of the APA

as amended.

List of Subjects in 40 CFR Parts 700,

720, 721, 723, and 725

Environmental protection,

Administrative practice and procedure,

Biotechnology, Chemicals, Hazardous

substances, Imports, Labeling,

Microorganisms, Occupational safety

and health, Reporting and

recordkeeping requirements, Significant

new use rule.

Dated: March 26, 1997.

Carol M. Browner,

Administrator.

Therefore, 40 CFR Chapter I is

amended as follows:

PART 700—[AMENDED]

1. In part 700:

a. The authority citation for part 700

continues to read as follows:

Authority: 15 U.S.C. 2625.

b. In § 700.43, by revising the

introductory text and the definition of

‘‘Section 5 notice’’ and adding two

definitions to read as follows:

§ 700.43 Definitions.

Definitions in section 3 of the Act (15

U.S.C. 2602), as well as definitions

contained in §§ 704.3, 720.3, and 725.3

of this chapter, apply to this subpart

unless otherwise specified in this

section. In addition, the following

definitions apply:

Consolidated microbial commercial

activity notice or consolidated MCAN

means any MCAN submitted to EPA

that covers more than one

microorganism (each being assigned a

separate MCAN number by EPA) as a

result of a prenotice agreement with

EPA.

* * * * *

Microbial commercial activity notice

or MCAN means any notice for

microorganisms submitted to EPA

pursuant to section 5(a)(1) of the Act in

accordance with subpart D of part 725

of this chapter.

* * * * *

Section 5 notice means any PMN,

consolidated PMN, intermediate PMN,

significant new use notice, exemption

notice, exemption application, any

MCAN or consolidated MCAN

submitted under section 5 of the Act.

* * * * *

c. In § 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:
17932 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

§ 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 §§ 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 § 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 § 725.25(b)

of this chapter.

(f) * * *

(3) The notice is incomplete under

either § 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 § 700.49 to read as

follows:

§ 700.49 Failure to remit fees.

EPA will not consider a section 5

notice to be complete unless the

appropriate certification under

§ 700.45(e) is included and until the

appropriate remittance under

§ 700.45(b) has been sent to EPA as

provided in § 700.45(e) and received by

EPA. EPA will notify the submitter that

the section 5 notice is incomplete in

accordance with §§ 720.65(c) and 725.33

of this chapter.

PART 720—[AMENDED]

2. In part 720:

a. The authority citation for part 720

continues to read as follows:

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

b. In § 720.1, by revising the first

sentence and adding a sentence to read

as follows:

§ 720.1 Scope.

This part establishes procedures for

the reporting of new chemical

substances by manufacturers and

importers under section 5 of the Toxic

Substances Control Act, 15 U.S.C. 2604.

This part applies to microorganisms

only to the extent provided by part 725

of this chapter. * * *

PART 721—[AMENDED]

3. In part 721:

a. The authority citation for part 721

continues to read as follows:

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

2625(c).

b. In § 721.1(a), by revising the first

sentence to read as follows:

§ 721.1 Scope and applicability.

This part identifies uses of chemical

substances, except for microorganisms

regulated under part 725 of this chapter,

which EPA has determined are

significant new uses under the authority

of section 5(a)(2) of the Toxic

Substances Control Act. * * *

PART 723—[AMENDED]

4. In part 723:

a. The authority citation for part 723

continues to read as follows:

Authority: 15 U.S.C. 2604.

b. In § 723.50, by revising the section

heading and adding paragraph (a)(3) to

read as follows:

§ 723.50 Chemical substances

manufactured in quantities of 10,000

kilograms or less per year, and chemical

substances with low environmental

releases and human exposures.

(a) * * *

(3) This section does not apply to

microorganisms subject to part 725 of

this chapter.

* * * * *

c. In § 723.175, by revising paragraph

(a)(1) to read as follows:

§ 723.175 Chemical substances used in or

for the manufacture or processing of

instant photographic and peel-apart film

articles.

(a) Purpose and scope. (1) This

section grants an exemption from the

premanufacture notice requirements of

section 5(a)(1)(A) of the Toxic

Substances Control Act (15 U.S.C.

2604(a)(1)(A)) for the manufacture and

processing of new chemical substances

used in or for the manufacture or

processing of instant photographic and

peel-apart film articles. This section

does not apply to microorganisms

subject to part 725 of this chapter.

* * * * *

d. In § 723.250, by revising paragraph

(a)(1) to read as follows:

§ 723.250 Polymers.

(a) Purpose and scope. (1) This

section grants an exemption from

certain of the premanufacture notice

requirements of section 5(a)(1)(A) of the

Toxic Substances Control Act (15 U.S.C.

2604(a)(1)(A)) for the manufacture of

certain polymers. This section does not

apply to microorganisms subject to part

725 of this chapter.

* * * * *

5. Part 725 is added to read as follows:

PART 725—REPORTING

REQUIREMENTS AND REVIEW

PROCESSES FOR MICROORGANISMS

Subpart A—General Provisions and

Applicability

Sec.

725.1 Scope and purpose.

725.3 Definitions.

725.8 Coverage of this part.

725.12 Identification of microorganisms for

Inventory and other listing purposes.

725.15 Determining applicability when

microorganism identity or use is confidential

or uncertain.

725.17 Consultation with EPA.

Subpart B—Administrative Procedures

725.20 Scope and purpose.

725.25 General administrative

requirements.

725.27 Submissions.

725.28 Notice that submission is not

required.

725.29 EPA acknowledgement of receipt of

submission.

725.32 Errors in the submission.

725.33 Incomplete submissions.

725.36 New information.

725.40 Notice in the Federal Register.

725.50 EPA review.

725.54 Suspension of the review period.

725.56 Extension of the review period.

725.60 Withdrawal of submission by the

submitter.

725.65 Recordkeeping.

725.67 Applications to exempt new

microorganisms from this part.

725.70 Compliance.

725.75 Inspections.

Subpart C—Confidentiality and Public

Access to Information

725.80 General provisions for

confidentiality claims.

725.85 Microorganism identity.

725.88 Uses of a microorganism.

725.92 Data from health and safety studies

of microorganisms.

725.94 Substantiation requirements.

725.95 Public file.

Subpart D—Microbial Commercial Activities

Notification Requirements

725.100 Scope and purpose.

725.105 Persons who must report.

725.110 Persons not subject to this subpart.

725.150 Procedural requirements for this

subpart.

725.155 Information to be included in the

MCAN.
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17933

725.160 Submission of health and

environmental effects data.

725.170 EPA review of the MCAN.

725.190 Notice of commencement of

manufacture or import.

Subpart E—Exemptions for Research and

Development Activities

725.200 Scope and purpose.

725.205 Persons who may report under this

subpart.

725.232 Activities subject to the

jurisdiction of other Federal programs or

agencies.

725.234 Activities conducted inside a

structure.

725.235 Conditions of exemption for

activities conducted inside a structure.

725.238 Activities conducted outside a

structure.

725.239 Use of specific microorganisms in

activities conducted outside a structure.

725.250 Procedural requirements for the

TERA.

725.255 Information to be included in the

TERA.

725.260 Submission of health and

environmental effects data.

725.270 EPA review of the TERA.

725.288 Revocation or modification of

TERA approval.

Subpart F—Exemptions for Test Marketing

725.300 Scope and purpose.

725.305 Persons who may apply under this

subpart.

725.350 Procedural requirements for this

subpart.

725.355 Information to be included in the

TME application.

725.370 EPA review of the TME

application.

Subpart G—General Exemptions for New

Microorganisms

725.400 Scope and purpose.

725.420 Recipient microorganisms.

725.421 Introduced genetic material.

725.422 Physical containment and control

technologies.

725.424 Requirements for the Tier I

exemption.

725.426 Applicability of the Tier I

exemption.

725.428 Requirements for the Tier II

exemption.

725.450 Procedural requirements for the

Tier II exemption.

725.455 Information to be included in the

Tier II exemption request.

725.470 EPA review of the Tier II

exemption request.

Subparts H—K [Reserved]

Subpart L—Additional Procedures for

Reporting on Significant New Uses of

Microorganisms

725.900 Scope and purpose.

725.910 Persons excluded from reporting

significant new uses.

725.912 Exemptions.

725.920 Exports and imports.

725.950 Additional recordkeeping

requirements.

725.975 EPA approval of alternative control

measures.

725.980 Expedited procedures for issuing

significant new use rules for microorganisms

subject to section 5(e) orders.

725.984 Modification or revocation of

certain notification requirements.

Subpart M—Significant New Uses for

Specific Microorganisms

725.1000 Scope.

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

2625.

Subpart A—General Provisions and

Applicability

§ 725.1 Scope and purpose.

(a) This part establishes all reporting

requirements under section 5 of TSCA

for manufacturers, importers, and

processors of microorganisms subject to

TSCA jurisdiction for commercial

purposes, including research and

development for commercial purposes.

New microorganisms for which

manufacturers and importers are

required to report under section

5(a)(1)(A) of TSCA are those that are

intergeneric. In addition, under section

5(a)(1)(B) of TSCA, manufacturers,

importers, and processors may be

required to report for any

microorganism that EPA determines by

rule is being manufactured, imported, or

processed for a significant new use.

(b) Any manufacturer, importer, or

processor required to report under

section 5 of TSCA (see § 725.100 for

new microorganisms and § 725.900 for

significant new uses) must file a

Microbial Commercial Activity Notice

(MCAN) with EPA, unless the activity is

eligible for a specific exemption as

described in this part. The general

procedures for filing MCANs are

described in subpart D of this part. The

exemptions from the requirement to file

a MCAN are for certain kinds of

contained activities (see §§ 725.424 and

725.428), test marketing activities (see

§ 725.300), and research and

development activities described in

paragraph (c) of this section.

(c) Any manufacturer, importer, or

processor required to file a MCAN for

research and development (R&D)

activities may instead file a TSCA

Experimental Release Application

(TERA) for a specific test (see

§ 725.250). A TERA is not required for

certain R&D activities; however a TERA

exemption does not extend beyond the

research and development stage, to

general commercial use of the

microorganism, for which compliance

with MCAN requirements is required.

The TERA exemptions are for R&D

activities subject to other Federal

agencies or programs (see § 725.232),

certain kinds of contained R&D

activities (see § 725.234), and R&D

activities using certain listed

microorganisms (see § 725.238).

(d) New microorganisms will be

added to the Inventory established

under section 8 of TSCA once a MCAN

has been received, the MCAN review

period has expired, and EPA receives a

Notice of Commencement (NOC)

indicating that manufacture or

importation has actually begun. New

microorganisms approved for use under

a TERA will not be added to the

Inventory until a MCAN has been

received, the MCAN review period has

expired, and EPA has received an NOC.

§ 725.3 Definitions.

Definitions in section 3 of the Act (15

U.S.C. 2602), as well as definitions

contained in §§ 704.3, 720.3, and 721.3

of this chapter, apply to this part unless

otherwise specified in this section. In

addition, the following definitions

apply to this part:

Consolidated microbial commercial

activity notice or consolidated MCAN

means any MCAN submitted to EPA

that covers more than one

microorganism (each being assigned a

separate MCAN number by EPA) as a

result of a prenotice agreement with

EPA.

Containment and/or inactivation

controls means any combination of

engineering, mechanical, procedural, or

biological controls designed and

operated to restrict environmental

release of viable microorganisms from a

structure.

Director means the Director of the

EPA Office of Pollution Prevention and

Toxics.

Exemption request means any

application submitted to EPA under

subparts E, F, or G of this part.

General commercial use means use

for commercial purposes other than

research and development.

Genome means the sum total of

chromosomal and extrachromosomal

genetic material of an isolate and any

descendants derived under pure culture

conditions from that isolate.

Health and safety study of a

microorganism or health and safety

study means any study of any effect of

a microorganism or microbial mixture

on health or the environment or on

both, including underlying data and

epidemiological studies, studies of

occupational exposure to a

microorganism or microbial mixture,

toxicological, clinical, and ecological, or

other studies of a microorganism or

microbial mixture, and any test

performed under the Act.

Microorganism identity is always part of

a health and safety study of a

microorganism.
17934 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

(1) It is intended that the term ‘‘health

and safety study of a microorganism’’ be

interpreted broadly. Not only is

information which arises as a result of

a formal, disciplined study included,

but other information relating to the

effects of a microorganism or microbial

mixture on health or the environment is

also included. Any data that bear on the

effects of a microorganism on health or

the environment would be included.

(2) Examples include:

(i) Tests for ecological or other

environmental effects on invertebrates,

fish, or other animals, and plants,

including: Acute toxicity tests, chronic

toxicity tests, critical life stage tests,

behavioral tests, algal growth tests, seed

germination tests, plant growth or

damage tests, microbial function tests,

bioconcentration or bioaccumulation

tests, and model ecosystem (microcosm)

studies.

(ii) Long- and short-term tests of

mutagenicity, carcinogenicity, or

teratogenicity; dermatoxicity;

cumulative, additive, and synergistic

effects; and acute, subchronic, and

chronic effects.

(iii) Assessments of human and

environmental exposure, including

workplace exposure, and impacts of a

particular microorganism or microbial

mixture on the environment, including

surveys, tests, and studies of: Survival

and transport in air, water, and soil;

ability to exchange genetic material with

other microorganisms, ability to

colonize human or animal guts, and

ability to colonize plants.

(iv) Monitoring data, when they have

been aggregated and analyzed to

measure the exposure of humans or the

environment to a microorganism.

(v) Any assessments of risk to health

and the environment resulting from the

manufacture, processing, distribution in

commerce, use, or disposal of the

microorganism.

Inactivation means that living

microorganisms are rendered nonviable.

Institutional Biosafety Committee

means the committees described in the

NIH Guidelines in section IV.B.2.

Intergeneric microorganism means a

microorganism that is formed by the

deliberate combination of genetic

material originally isolated from

organisms of different taxonomic

genera.

(1) The term ‘‘intergeneric

microorganism’’ includes a

microorganism which contains a mobile

genetic element which was first

identified in a microorganism in a genus

different from the recipient

microorganism.

(2) The term ‘‘intergeneric

microorganism’’ does not include a

microorganism which contains

introduced genetic material consisting

of only well-characterized, non-coding

regulatory regions from another genus.

Introduced genetic material means

genetic material that is added to, and

remains as a component of, the genome

of the recipient.

Manufacture, import, or process for

commercial purposes means:

(1) To import, produce, manufacture,

or process with the purpose of obtaining

an immediate or eventual commercial

advantage for the manufacturer,

importer, or processor, and includes,

among other things, ‘‘manufacture’’ or

‘‘processing’’ of any amount of a

microorganism or microbial mixture:

(i) For commercial distribution,

including for test marketing.

(ii) For use by the manufacturer,

including use for product research and

development or as an intermediate.

(2) The term also applies to

substances that are produced

coincidentally during the manufacture,

processing, use, or disposal of another

microorganism or microbial mixture,

including byproducts that are separated

from that other microorganism or

microbial mixture and impurities that

remain in that microorganism or

microbial mixture. Byproducts and

impurities without separate commercial

value are nonetheless produced for the

purpose of obtaining a commercial

advantage, since they are part of the

manufacture or processing of a

microorganism for commercial

purposes.

Microbial commercial activity notice

or MCAN means a notice for

microorganisms submitted to EPA

pursuant to section 5(a)(1) of the Act in

accordance with subpart D of this part.

Microbial mixture means any

combination of microorganisms or

microorganisms and other chemical

substances, if the combination does not

occur in nature and is not an article.

Microorganism means an organism

classified, using the 5-kingdom

classification system of Whittacker, in

the kingdoms Monera (or Procaryotae),

Protista, Fungi, and the Chlorophyta

and the Rhodophyta of the Plantae, and

a virus or virus-like particle.

Mobile genetic element or MGE means

an element of genetic material that has

the ability to move genetic material

within and between organisms. ‘‘Mobile

genetic elements’’ include all plasmids,

viruses, transposons, insertion

sequences, and other classes of elements

with these general properties.

New microorganism means a

microorganism not included on the

Inventory.

NIH Guidelines means the National

Institutes of Health (NIH) ‘‘Guidelines

for Research Involving Recombinant

DNA Molecules’’ (July 5, 1994).

Non-coding regulatory region means a

segment of introduced genetic material

for which:

(1) The regulatory region and any

inserted flanking nucleotides do not

code for protein, peptide, or functional

ribonucleic acid molecules.

(2) The regulatory region solely

controls the activity of other regions that

code for protein or peptide molecules or

act as recognition sites for the initiation

of nucleic acid or protein synthesis.

Small quantities solely for research

and development (or ‘‘small quantities

solely for purposes of scientific

experimentation or analysis or research

on, or analysis of, such substance or

another substance, including such

research or analysis for development of

a product’’) means quantities of a

microorganism manufactured, imported,

or processed or proposed to be

manufactured, imported, or processed

solely for research and development

that meet the requirements of § 725.234.

Structure means a building or vessel

which effectively surrounds and

encloses the microorganism and

includes features designed to restrict the

microorganism from leaving.

Submission means any MCAN or

exemption request submitted to EPA

under this part.

Technically qualified individual

means a person or persons:

(1) Who, because of education,

training, or experience, or a

combination of these factors, is capable

of understanding the health and

environmental risks associated with the

microorganism which is used under his

or her supervision,

(2) Who is responsible for enforcing

appropriate methods of conducting

scientific experimentation, analysis, or

microbiological research to minimize

such risks, and

(3) Who is responsible for the safety

assessments and clearances related to

the procurement, storage, use, and

disposal of the microorganism as may be

appropriate or required within the scope

of conducting a research and

development activity.

TSCA Experimental Release

Application or TERA means an

exemption request for a research and

development activity, which is not

eligible for a full exemption from

reporting under § 725.232, 725.234, or

725.238, submitted to EPA in

accordance with subpart E of this part.

Well-characterized for introduced

genetic material means that the

following have been determined:
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17935

(1) The function of all of the products

expressed from the structural gene(s).

(2) The function of sequences that

participate in the regulation of

expression of the structural gene(s).

(3) The presence or absence of

associated nucleotide sequences and

their associated functions, where

associated nucleotide sequences are

those sequences needed to move genetic

material including linkers,

homopolymers, adaptors, transposons,

insertion sequences, and restriction

enzyme sites.

§ 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

§ 725.3, are subject to the requirements

of this part.

(b) Microorganisms automatically

included on the Inventory.

Microorganisms that are not intergeneric

are automatically included on the

Inventory.

(c) Microorganisms not subject to this

part. The following microorganisms are

not subject to this part, either because

they are not subject to jurisdiction

under the Act or are not subject to

reporting under section 5 of the Act.

(1) Any microorganism which would

be excluded from the definition of

‘‘chemical substance’’ in section 3 of the

Act and § 720.3(e) of this chapter.

(2) Any microbial mixture as defined

in § 725.3. This exclusion applies only

to a microbial mixture as a whole and

not to any microorganisms and other

chemical substances which are part of

the microbial mixture.

(3) Any microorganism that is

manufactured and processed solely for

export if the following conditions are

met:

(i) The microorganism is labeled in

accordance with section 12(a)(1)(B) of

the Act, when the microorganism is

distributed in commerce.

(ii) The manufacturer and processor

can document at the commencement of

manufacturing or processing that the

person to whom the microorganism will

be distributed intends to export it or

process it solely for export as defined in

§ 721.3 of this chapter.

§ 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.

§ 725.15 Determining applicability when

microorganism identity or use is

confidential or uncertain.

(a) Consulting EPA. Persons intending

to conduct activities involving

microorganisms may determine their

obligations under this part by consulting

the Inventory or the microorganisms

and uses specified in § 725.239 or in

subpart M of this part. This section

establishes procedures for EPA to assist

persons in determining whether the

microorganism or the use is listed on

the Inventory, in § 725.239 or in subpart

M of this part.

(1) Confidential identity or use. In

some cases it may not be possible to

directly determine if a specific

microorganism is listed, because

portions of that entry may contain

generic information to protect

confidential business information (CBI).

If any portion of the microorganism’s

identity or use has been claimed as CBI,

that portion does not appear on the

public version of the Inventory, in

§ 725.239 or in subpart M of this part.

Instead, it is contained in a confidential

version held in EPA’s Confidential

Business Information Center (CBIC). The

public versions contain generic

information which masks the

confidential business information. A

person who intends to conduct an

activity involving a microorganism or

use whose entry is described with

generic information will need to inquire

of EPA whether the unreported

microorganism or use is on the

confidential version.

(2) Uncertain microorganism identity.

The current state of scientific

knowledge leads to some imprecision in

describing a microorganism. As the state

of knowledge increases, EPA will be

developing policies to determine

whether one microorganism is

equivalent to another. Persons intending

to conduct activities involving

microorganisms may inquire of EPA

whether the microorganisms they intend

to manufacture, import, or process are

equivalent to specific microorganisms

described on the Inventory, in

§ 725.239, or in subpart M of this part.

(b) Requirement of bona fide intent.

(1) EPA will answer the inquiries

described in paragraph (a) of this

section only if the Agency determines

that the person has a bona fide intent to

conduct the activity for which reporting

is required or for which any exemption

may apply.

(2) To establish a bona fide intent to

manufacture, 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

§ 725.12.

(ii) A signed statement certifying that

the submitter intends to manufacture,

import, or process the microorganism

for commercial purposes.

(iii) A description of research and

development activities conducted with

the microorganism to date,

demonstration of the submitter’s ability

to produce or obtain the microorganism

from a foreign manufacturer, and the

purpose for which the person will
17936 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

manufacture, import, or process the

microorganism.

(iv) An indication of whether a related

microorganism was previously reviewed

by EPA to the extent known by the

submitter.

(v) A specific description of the major

intended application or use of the

microorganism.

(c) If an importer or processor cannot

provide all the information required by

paragraph (b) of this section, because it

is claimed as confidential business

information by its foreign manufacturer

or supplier, the foreign manufacturer or

supplier may supply the information

directly to EPA.

(d) EPA will review the information

submitted by the manufacturer,

importer, or processor under this

paragraph to determine whether that

person has shown a bona fide intent to

manufacture, import, or process the

microorganism. If necessary, EPA will

compare this information to the

information requested for the

confidential microorganism under

§ 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 § 725.239 or in subpart M

of this part, EPA will notify the

person(s) who originally reported the

microorganism that another person

(whose identity will remain

confidential, if so requested) has

demonstrated a bona fide intent to

manufacture, import, or process the

microorganism and therefore was told

that the microorganism is on the

Inventory, in § 725.239, or in subpart M

of this part.

(g) A disclosure to a person with a

bona fide intent to manufacture, import,

or process a particular microorganism

that the microorganism is on the

Inventory, in § 725.239, or in subpart M

of this part will not be considered a

public disclosure of confidential

business information under section 14

of the Act.

(h) EPA will answer an inquiry on

whether a particular microorganism is

subject to this part within 30 days after

receipt of a complete submission under

paragraph (b) of this section.

§ 725.17 Consultation with EPA.

Persons may consult with EPA, either

in writing or by telephone, about their

obligations under this part. Written

consultation is preferred. Written

inquiries should be sent to the following

address: Environmental Assistance

Division (7408), Office of Pollution

Prevention and Toxics, U.S.

Environmental Protection Agency, 401

M St., SW., Washington, DC 20460,

ATTN: Biotechnology Notice

Consultation. Persons wishing to

consult with EPA by telephone should

call (202) 554–1404; hearing impaired

TDD (202) 554–0551 or e-mail: TSCAHotline@epamail.epa.gov.

Subpart B—Administrative Procedures

§ 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.

§ 725.25 General administrative

requirements.

(a) General. (1) Each person who is

subject to the notification provisions of

this part must complete, sign, and

submit a MCAN or exemption request

containing the information as required

for the appropriate submission under

this part. Except as otherwise provided,

each submission must include all

referenced attachments. All information

in the submission (unless certain

attachments appear in the open

scientific literature) must be in English.

All information submitted must be true

and correct.

(2) In addition to specific information

required, the submitter should submit

all information known to or reasonably

ascertainable by the submitter that

would permit EPA to make a reasoned

evaluation of the human health and

environmental effects of the

microorganism and any microbial

mixture or article that may contain the

microorganism.

(b) Certification. Persons submitting

MCANs and exemption requests to EPA

under this part, and material related to

their reporting obligations under this

part, must attach the following

statement to any information submitted

to EPA. This statement must be signed

and dated by an authorized official of

the submitter:

I certify that to the best of my knowledge

and belief: The company named in this

submission intends to manufacture, import,

or process for a commercial purpose, other

than in small quantities solely for research

and development, the microorganism

identified in this submission. All information

provided in this submission is complete and

truthful as of the date of submission. I am

including with this submission all test data

in my possession or control and a description

of all other data known to or reasonably

ascertainable by me as required by 40 CFR

725.160 or 725.260.

(c) Where to submit information

under this part. Persons submitting

MCANs and exemption requests to EPA

under this part, and material related to

their reporting obligations under this

part, must send them to: TSCA

Document Processing Center (7407),

Rm. L–100, Office of Pollution

Prevention and Toxics, U.S.

Environmental Protection Agency, 401

M St., SW., Washington, DC 20460.

(d) General requirements for

submission of data. (1) Submissions

under this part must include the

information described in § 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 § 725.160 or

725.260, as appropriate, the submission

must also include any test data in the

submitter’s possession or control and

descriptions of other data which are

known to or reasonably ascertainable by

the submitter and which concern the

health and environmental effects of the

microorganism.

(e) Agency or joint submissions. (1) A

manufacturer or importer may designate

an agent to submit the MCAN or

exemption request. Both the

manufacturer or importer and the agent

must sign the certification required in

paragraph (b) of this section.

(2) A manufacturer or importer may

authorize another person (e.g., a foreign

manufacturer or supplier, or a toll

manufacturer) to report some of the

information required in the MCAN or

exemption request to EPA on its behalf.

If separate portions of a joint submission

are not submitted together, the

submitter must indicate which

information will be supplied by another

person and identify that person. The

manufacturer or importer and any other

person supplying the information must

sign the certification required by

paragraph (b) of this section.

(3) If EPA receives a submission

which does not include the information

required, which the submitter indicates

that it has authorized another person to

provide, the review period will not

begin until EPA receives all of the

required information.

(f) Microorganisms subject to a section

4 test rule. (1) Except as provided in

paragraph (f)(3) of this section, if a
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17937

person intends to manufacture or import

a new microorganism which is subject

to the notification requirements of this

part, and the microorganism is subject

to a test rule promulgated under section

4 of the Act before the notice is

submitted, section 5(b)(1) of the Act

requires the person to submit the test

data required by the testing rule with

the notice. The person must submit the

data in the form and manner specified

in the test rule and in accordance with

§ 725.160. If the person does not submit

the test data, the submission is

incomplete and EPA will follow the

procedures in § 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

§ 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 § 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 § 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.

§ 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 §§ 725.150 through

725.160.

(b) Requirements specific to TERAs

are described in §§ 725.250 through

725.260.

(c) Requirements specific to test

marketing exemptions (TMEs) are

described in §§ 725.350 and 725.355.

(d) Requirements specific to Tier I and

Tier II exemptions for certain general

commercial uses are described in

§§ 725.424 through 725.470.

(e) Additional requirements specific

to significant new uses for

microorganisms are described at

§ 725.950.

§ 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.

§ 725.29 EPA acknowledgement of receipt

of submission.

(a) EPA will acknowledge receipt of

each submission by sending the

submitter a letter that identifies the

number assigned to each MCAN or

exemption request and the date on

which the review period begins. The

review period will begin on the date the

MCAN or exemption request is received

by the Office of Pollution Prevention

and Toxics Document Control Officer.

(b) The acknowledgement does not

constitute a finding by EPA that the

submission is in compliance with this

part.

§ 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.

§ 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 § 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

§ 725.160 or 725.260, as appropriate.

(5) The submitter does not provide

information required by § 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 § 725.80(b)(2).

(ii) Comply with the substantiation

requirements as described in § 725.94.
17938 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

(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 § 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 § 725.25(g).

(9) For MCANs, the submitter does

not remit the fees required by

§ 700.45(b)(1) or (b)(2)(vi) of this

chapter.

(b)(1) If EPA receives an incomplete

submission under this part, the Director,

or a designee, will notify the submitter

within 30 days of receipt that the

submission is incomplete and that the

review period will not begin until EPA

receives a complete submission.

(2) If EPA obtains additional

information during the review period

for any submission that indicates the

original submission was incomplete, the

Director, or a designee, may declare the

submission incomplete within 30 days

after EPA obtains the additional

information and so notify the submitter.

(c) The notification that a submission

is incomplete under paragraph (b) of

this section will include:

(1) A statement of the basis of EPA’s

determination that the submission is

incomplete.

(2) The requirements for correcting

the incomplete submission.

(3) Information on procedures under

paragraph (d) of this section for filing

objections to the determination or

requesting modification of the

requirements for completing the

submission.

(d) Within 10 days after receipt of

notification by EPA that a submission is

incomplete, the submitter may file

written objections requesting that EPA

accept the submission as complete or

modify the requirements necessary to

complete the submission.

(e)(1) EPA will consider the objections

filed by the submitter. The Director, or

a designee, will determine whether the

submission was complete or

incomplete, or whether to modify the

requirements for completing the

submission. EPA will notify the

submitter in writing of EPA’s response

within 10 days of receiving the

objections.

(2) If the Director, or a designee,

determines, in response to the objection,

that the submission was complete, the

review period will be deemed

suspended on the date EPA declared the

submission incomplete, and will resume

on the date that the submission is

declared complete. The submitter need

not correct the submission as EPA

originally requested. If EPA can

complete its review within the review

period beginning on the date of the

submission, the Director, or a designee,

may inform the submitter that the

running of the review period will

resume on the date EPA originally

declared it incomplete.

(3) If the Director, or a designee,

modifies the requirements for

completing the submission or concurs

with EPA’s original determination, the

review period will begin when EPA

receives a complete submission.

(f) If EPA discovers at any time that

a person submitted materially false or

misleading statements in information

submitted under this part, EPA may find

that the submission was incomplete

from the date it was submitted, and take

any other appropriate action.

§ 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 § 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.

§ 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 § 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

§ 725.88 will be published.

(3) A list of information submitted in

accordance with § 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.

§ 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 § 725.33, unless the Agency

extends the review period under section

5(c) of the Act and § 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 § 725.33, unless the Agency

extends the review period under

§ 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.

§ 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

§ 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
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17939

longer suspension, the Document

Control Officer for the Office of

Pollution Prevention and Toxics must

receive written confirmation of the oral

request. The review period is suspended

as of the date of the oral request.

(2) If the submitter has not made a

previous oral request, the running of the

review period is suspended as of the

date of receipt of the written request by

the Document Control Officer for the

Office of Pollution Prevention and

Toxics.

§ 725.56 Extension of the review period.

(a) At any time during the review

period, EPA may unilaterally determine

that good cause exists to extend the

review period specified for MCANs, or

the exemption requests.

(b) If EPA makes such a

determination, EPA:

(1) Will notify the submitter that EPA

is extending the review period for a

specified length of time and state the

reasons for the extension.

(2) For MCANs, EPA may issue a

notice for publication in the Federal

Register which states that EPA is

extending the review period and gives

the reasons for the extension.

(c) The total period of the extension

may be for a period of up to the same

length of time as specified for each type

of submission in § 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 § 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.

§ 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

§ 725.25(c). The withdrawal is effective

upon receipt of the statement by the

Document Control Officer.

(b) If a manufacturer, importer, or

processor who withdrew a submission

later resubmits a submission for the

same microorganism, a new review

period begins.

§ 725.65 Recordkeeping.

(a) General provisions. (1) Any person

who submits a notice under this part

must retain documentation of

information in the submission,

including:

(i) Any data in the submitter’s

possession or control; and

(ii) Records of production volume for

the first 3 years of manufacture, import,

or processing.

(2) Any person who submits a notice

under this part must retain

documentation of the date of

commencement of testing, manufacture,

import, or processing.

(3) Any person who is exempt from

some or all of the reporting

requirements of this part must retain

documentation that supports the

exemption.

(4) All information required by this

section must be retained for 3 years

from the date of commencement of each

activity for which records are required

under this part.

(b) Specific requirements. In addition

to the requirements of paragraph (a) of

this section, specific recordkeeping

requirements included in certain

subparts must also be followed.

(1) Additional recordkeeping

requirements for activities conducted

inside a structure are set forth in

§ 725.235(h).

(2) Additional recordkeeping

requirements for TERAs are set forth in

§ 725.250(f).

(3) Additional recordkeeping

requirements for TMEs are set forth in

§ 725.350(c).

(4) Additional recordkeeping

requirements for Tier I exemptions

under subpart G of this part are set forth

in § 725.424(a)(5).

(5) Additional recordkeeping

requirements for Tier II exemptions

under subpart G of this part are set forth

in § 725.450(d).

(6) Additional recordkeeping

requirements for significant new uses of

microorganisms reported under subpart

L of this part are set forth in § 725.850.

Recordkeeping requirements may also

be included when a microorganism and

significant new use are added to subpart

M of this part.

§ 725.67 Applications to exempt new

microorganisms from this part.

(a) Submission. (1) Any manufacturer

or importer of a new microorganism

may request, under section 5(h)(4) of the

Act, an exemption, in whole or in part,

from this part by sending a Letter of

Application to the Chief, New

Chemicals Branch, Chemical Control

Division, Office of Pollution Prevention

and Toxics, U.S. Environmental

Protection Agency, 401 M St., SW.,

Washington, DC 20460.

(2) General provisions. The Letter of

Application should provide information

to show that any activities affected by

the requested exemption will not

present an unreasonable risk of injury to

health or the environment. This

information should include data

described in the following paragraphs.

(i) The effects of the new

microorganism on health and the

environment.

(ii) The magnitude of exposure of

human beings and the environment to

the new microorganism.

(iii) The benefits of the new

microorganism for various uses and the

availability of substitutes for such uses.

(iv) The reasonably ascertainable

economic consequences of granting or

denying the exemption, including

effects on the national economy, small

business, and technological innovation.

(3) Specific requirements. In addition

to the requirements of paragraph (a)(2)

of this section, the specific information

requirements of the relevant subpart

under which the exemption is sought

should be met.

(i) Exemption from MCAN reporting

under subpart D. Information

requirements are set forth in §§ 725.155

and 725.160.

(ii) Exemption from TERA reporting

under subpart E. Information

requirements are set forth in §§ 725.255

and 725.260.

(iii) Listing a recipient microorganism

as eligible for exemption under subpart

G. Information regarding the following

criteria should be addressed in an

application to list a recipient

microorganism under § 725.420:

(A) Identification and classification of

the microorganism using available

genotypic and phenotypic information;

(B) Information to evaluate the

relationship of the microorganism to

any other closely related

microorganisms which have a potential

for adverse effects on health or the

environment;

(C) A history of safe commercial use

for the microorganism;

(D) Commercial uses indicating that

the microorganism products might be

subject to TSCA;

(E) Studies which indicate the

potential for the microorganism to cause

adverse effects to health or the

environment; and
17940 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

(F) Studies which indicate the

survival characteristics of the

microorganism in the environment.

(b) Processing of the Letter of

Application by EPA—(1) Grant of the

Application. If, after consideration of

the Letter of Application and any other

relevant information available to EPA,

the Assistant Administrator for

Prevention, Pesticides and Toxic

Substances makes a preliminary

determination that the new

microorganism will not present an

unreasonable risk of injury to health or

the environment, the Assistant

Administrator will propose a rule to

grant the exemption using the

applicable procedures in part 750 of this

chapter.

(2) Denial of the application. If the

Assistant Administrator decides that the

preliminary determination described in

paragraph (b)(1) of this section cannot

be made, the application will be denied

by sending the applicant a written

statement with the Assistant

Administrator’s reasons for denial.

(c) Processing of the exemption—(1)

Unreasonable risk standard. Granting a

section 5(h)(4) exemption requires a

determination that the activities will not

present an unreasonable risk of injury to

health or the environment.

(i) An unreasonable risk

determination under the Act is an

administrative judgment that requires

balancing of the harm to health or the

environment that a chemical substance

may cause and the magnitude and

severity of that harm, against the social

and economic effects on society of EPA

action to reduce that harm.

(ii) A determination of unreasonable

risk under section 5(h)(4) of the Act will

examine the reasonably ascertainable

economic and social consequences of

granting or denying the exemption after

consideration of the effect on the

national economy, small business,

technological innovation, the

environment, and public health.

(2) Grant of the exemption. The

exemption will be granted if the

Assistant Administrator determines,

after consideration of all relevant

evidence presented in the rulemaking

proceeding described in paragraph (b)(1)

of this section, that the new

microorganism will not present an

unreasonable risk of injury to health or

the environment.

(3) Denial of the exemption. The

exemption will be denied if the

Assistant Administrator determines,

after consideration of all relevant

evidence presented in the rulemaking

proceeding described in paragraph (b)(1)

of this section, that the determination

described in paragraph (c)(2) of this

section cannot be made. A final decision

terminating the rulemaking proceeding

will be published in the Federal

Register.

§ 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 § 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).

§ 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

§ 725.80 General provisions for

confidentiality claims.

(a) A person may assert a claim of

confidentiality for any information

submitted to EPA under this part.

However,

(1) Any person who asserts a claim of

confidentiality for portions of the

specific microorganism identity must

provide the information as described in

§ 725.85.

(2) Any person who asserts a claim of

confidentiality for a use of a

microorganism must provide the

information as described in § 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 § 725.92.

(b) Any claim of confidentiality must

accompany the information when it is

submitted to EPA.

(1) When a person submits any

information under this part, including

any attachments, for which claims of

confidentiality are made, the claim(s)

must be asserted by circling the specific

information which is claimed and

marking the page on which that

information appears with an appropriate

designation such as ‘‘trade secret,’’

‘‘TSCA CBI,’’ or ‘‘confidential business

information.’’

(2) If any information is claimed

confidential, the person must submit

two copies of the document including

the claimed information.

(i) One copy of the document must be

complete. In that copy, the submitter

must mark the information which is

claimed as confidential in the manner

prescribed in paragraph (b)(1) of this

section.

(ii) The second copy must be

complete except that all information

claimed as confidential in the first copy

must be deleted. EPA will place the

second copy in the public file.

(iii) If the submitter does not provide

the second copy, the submission is

incomplete and the review period does

not begin to run until EPA receives the

second copy, in accordance with

§ 725.33.

(iv) Any information contained within

the copy submitted under paragraph

(b)(2)(ii) of this section which has been

in the public file for more than 30 days

will be presumed to be in the public

domain, notwithstanding any assertion

of confidentiality made under this

section.

(3) A person who submits information

to EPA under this part must reassert a

claim of confidentiality and substantiate

the claim each time the information is

submitted to EPA.

(c) Any person asserting a claim of

confidentiality under this part must

substantiate each claim in accordance

with the requirements in § 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.
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17941

(e) If a submitter does not assert a

claim of confidentiality for information

at the time it is submitted to EPA, EPA

may make the information public and

place it in the public file without further

notice to the submitter.

§ 725.85 Microorganism identity.

(a) Claims applicable to the period

prior to commencement of manufacture

or import for general commercial use—

(1) When to make a claim. (i) A person

who submits information to EPA under

this part may assert a claim of

confidentiality for portions of the

specific microorganism identity at the

time of submission of the information.

This claim will apply only to the period

prior to the commencement of

manufacture or import for general

commercial use.

(ii) A person who submits information

to EPA under this part must reassert a

claim of confidentiality and substantiate

the claim each time the information is

submitted to EPA. For example, if a

person claims certain information

confidential in a TERA submission and

wishes the same information to remain

confidential in a subsequent TERA or

MCAN submission, the person must

reassert and resubstantiate the claim in

the subsequent submission.

(2) Assertion of claim. (i) A submitter

may assert a claim of confidentiality

only if the submitter believes that public

disclosure prior to commencement of

manufacture or import for general

commercial use of the fact that anyone

is initiating research and development

activities pertaining to the specific

microorganism or intends to

manufacture or import the specific

microorganism for general commercial

use would reveal confidential business

information. Claims must be

substantiated in accordance with the

requirements of § 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 § 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

§ 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 § 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 § 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

§ 725.12.

(iv) Provide a detailed written

substantiation of the claim, in

accordance with the requirements of

§ 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

§ 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
17942 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

§ 725.15(b) to determine whether the

particular microorganism is included on

the confidential Inventory.

(iii) Upon receipt of a request

described in § 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.

§ 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 § 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.

§ 725.92 Data from health and safety

studies of microorganisms.

(a) Information other than specific

microorganism identity. Except as

provided in paragraph (b) of this

section, EPA will deny any claim of

confidentiality with respect to

information included in a health and

safety study of a microorganism, unless

the information would disclose

confidential business information

concerning:

(1) Processes used in the manufacture

or processing of a microorganism.

(2) Information which is not in any

way related to the effects of a

microorganism on health or the

environment, such as, the name of the

submitting company, cost or other

financial data, product development or

marketing plans, and advertising plans,

for which the person submits a claim of

confidentiality in accordance with

§ 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

§ 725.85(a). The submitter must

substantiate each claim in accordance

with the requirements of § 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

§ 725.85(b). The submitter must

substantiate each claim in accordance

with the requirements of § 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 § 725.85.

§ 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 § 725.33.

(2) TERA requirements. Any person

who submits a TERA, should strictly

limit confidentiality claims to that

information which is confidential and

proprietary to the business. If any

information in such a submission is

claimed as confidential business

information, the submitter must have

available for each of those claims, and
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17943

agree to furnish to EPA upon request,

written answers to the questions in

paragraphs (d) and (e) of this section.

(b) Claims applicable to the period

after commencement of manufacture or

import for general commercial use. (1) If

a submitter claimed portions of the

microorganism identity confidential in

the MCAN and wants the identity to be

listed on the confidential Inventory, the

claim must be reasserted and

substantiated at the time the Notice of

Commencement (NOC) is submitted

under § 725.190. Otherwise, EPA will

list the specific microorganism identity

on the public Inventory.

(2) The submitter must substantiate

the claim for confidentiality of the

microorganism identity by answering all

of the questions in paragraphs (c), (d),

and (e) in this section. In addition, the

following questions must be answered:

(i) What harmful effects to the

company’s or institution’s competitive

position, if any, would result if EPA

publishes on the Inventory the identity

of the microorganism? How could a

competitor use such information given

the fact that the identity of the

microorganism otherwise would appear

on the TSCA Inventory with no link

between the microorganism and the

company or institution? How

substantial would the harmful effects of

disclosure be? What is the causal

relationship between the disclosure and

the harmful effects?

(ii) Has the identity of the

microorganism been kept confidential to

the extent that competitors do not know

it is being manufactured or imported for

general commercial use by anyone?

(c) General questions. The following

questions must be answered in detail for

each confidentiality claim:

(1) For what period of time is a claim

of confidentiality being asserted? If the

claim is to extend until a certain event

or point in time, indicate that event or

time period. Explain why the

information should remain confidential

until such point.

(2) Briefly describe any physical or

procedural restrictions within the

company or institution relating to the

use and storage of the information

claimed as confidential. What other

steps, if any, apply to use or further

disclosure of the information?

(3) Has the information claimed as

confidential been disclosed to

individuals outside of the company or

institution? Will it be disclosed to such

persons in the future? If so, what

restrictions, if any, apply to use or

further disclosure of the information?

(4) Does the information claimed as

confidential appear, or is it referred to,

in any of the following questions? If the

answer is yes to any of these questions,

indicate where the information appears

and explain why it should nonetheless

be treated as confidential.

(i) Advertising or promotional

materials for the microorganism or the

resulting end product?

(ii) Material safety data sheets or other

similar materials for the microorganism

or the resulting end product?

(iii) Professional or trade

publications?

(iv) Any other media available to the

public or to competitors?

(v) Patents?

(vi) Local, State, or Federal agency

public files?

(5) Has EPA, another Federal agency,

a Federal court, or a State made any

confidentiality determination regarding

the information claimed as confidential?

If so, provide copies of such

determinations.

(6) For each type of information

claimed confidential, describe the harm

to the company’s or institution’s

competitive position that would result if

this information were disclosed. Why

would this harm be substantial? How

could a competitor use such

information? What is the causal

connection between the disclosure and

harm?

(7) If EPA disclosed to the public the

information claimed as confidential,

how difficult would it be for the

competitor to enter the market for the

resulting product? Consider such

constraints as capital and marketing

cost, specialized technical expertise, or

unusual processes.

(d) Microorganism identity and

production method. If confidentiality

claims are asserted for the identity of

the microorganism or information on

how the microorganism is produced, the

following questions must be answered:

(1) Has the microorganism or method

of production been patented in the U.S.

or elsewhere? If so, why is

confidentiality necessary?

(2) Does the microorganism leave the

site of production or testing in a form

which is accessible to the public or to

competitors? What is the cost to a

competitor, in time and money, to

develop appropriate use conditions?

What factors facilitate or impede

product analysis?

(3) For each additional type of

information claimed as confidential,

explain what harm would result from

disclosure of each type of information if

the identity of the microorganism were

to remain confidential.

(e) Health and safety studies of

microorganisms. If confidentiality

claims are asserted for information in a

health or safety study of a

microorganism, the following questions

must be answered:

(1) Would the disclosure of the

information claimed confidential reveal:

confidential process information, or

information unrelated to the effects of

the microorganism on health and the

environment. Describe the causal

connection between the disclosure and

harm.

(2) Does the company or institution

assert that disclosure of the

microorganism identity is not necessary

to interpret any health and safety

studies which have been submitted? If

so, explain how a less specific identity

would be sufficient to interpret the

studies.

§ 725.95 Public file.

All information submitted, including

any health and safety study of a

microorganism and other supporting

documentation, will become part of the

public file for that submission, unless

such materials are claimed confidential.

In addition, EPA may add materials to

the public file, unless such materials are

claimed confidential. Any of the

nonconfidential material described in

this subpart will be available for public

inspection in the TSCA Public Docket

Office, Rm. NE–B607, 401 M St., SW.,

Washington, DC, between the hours of

noon to 4 p.m., Monday through Friday,

excluding legal holidays.

Subpart D—Microbial Commercial Activities

Notification Requirements

§ 725.100 Scope and purpose.

(a) This subpart establishes

procedures for submission of a notice to

EPA under section 5(a) of the Act for

persons who manufacture, import, or

process microorganisms for commercial

purposes. This notice is called a

Microbial Commercial Activity Notice

(MCAN). It is expected that MCANs will

in general only be submitted for

microorganisms intended for general

commercial use. Persons who

manufacture, import, or process a

microorganism in small quantities

solely for research and development as

defined in § 725.3 are not required to

submit a notice to EPA. Persons who

manufacture, import, or process a

microorganism for research and

development activities that do not fit

the definition of small quantities solely

for research and development may

nonetheless qualify for more limited

reporting requirements in Subpart E,

including the TERA which can be used

for review of research and development

involving environmental release.

(b) Persons subject to MCAN

submission are described in § 725.105.
17944 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

(c) Exclusions and exemptions

specific to MCAN submissions are

described in § 725.110.

(d) Submission requirements

applicable specifically to MCANs are

described at § 725.150.

(e) Data requirements for MCANs are

set forth in §§ 725.155 and 725.160.

(f) EPA review procedures specific to

MCANs are set forth in § 725.170.

(g) Subparts A through C of this part

apply to any MCAN submitted under

this subpart.

§ 725.105 Persons who must report.

(a) Manufacturers of new

microorganisms. (1) MCAN submission

is required for any person who intends

to manufacture for commercial purposes

in the United States a new

microorganism. Exclusions are

described in § 725.110.

(2) If a person contracts with a

manufacturer to produce or process a

new microorganism and the

manufacturer produces or processes the

microorganism exclusively for that

person, and that person specifies the

identity of the microorganism, and

controls the total amount produced and

the basic technology for the plant

process, then that person must submit

the MCAN. If it is unclear who must

report, EPA should be contacted to

determine who must submit the MCAN.

(3) Only manufacturers that are

incorporated, licensed, or doing

business in the United States may

submit a MCAN.

(b) Importers of new microorganisms.

(1) MCAN submission is required for a

person who intends to import into the

United States for commercial purposes

a new microorganism. Exclusions are

described in § 725.110.

(2) When several persons are involved

in an import transaction, the MCAN

must be submitted by the principal

importer. If no one person fits the

principal importer definition in a

particular transaction, the importer

should contact EPA to determine who

must submit the MCAN for that

transaction.

(3) Except as otherwise provided in

paragraph (b)(4) of this section, the

provisions of this subpart D apply to

each person who submits a MCAN for

a new microorganism which such

person intends to import for a

commercial purpose. In addition, each

importer must comply with paragraph

(b)(4) of this section.

(4) EPA will hold the principal

importer, or the importer that EPA

determines must submit the MCAN

when there is no principal importer

under paragraph (b)(2) of this section,

liable for complying with this part, for

completing the MCAN, and for the

completeness and truthfulness of all

information which it submits.

(c) Manufacturers, importers, or

processors of microorganisms for a

significant new use. MCAN submission

is required for any person who intends

to manufacture, import, or process for

commercial purposes a microorganism

identified as having one or more

significant new uses in subpart M of this

part, and who intends either to engage

in a designated significant new use of

the microorganism or intends to

distribute it in commerce. Persons

excluded from reporting on significant

new uses of microorganisms and

additional procedures for reporting are

described in subpart L of this part.

§ 725.110 Persons not subject to this

subpart.

Persons are not subject to the

requirements of this subpart for the

following activities:

(a) Manufacturing, importing, or

processing solely for research and

development microorganisms that meet

the requirements for an exemption

under subpart E of this part.

(b) Manufacturing, importing, or

processing microorganisms for test

marketing activities which have been

granted an exemption under subpart F

of this part.

(c) Manufacturing or importing new

microorganisms under the conditions of

a Tier I or Tier II exemption under

subpart G of this part.

§ 725.150 Procedural requirements for this

subpart.

General requirements for all MCANs

under this part are contained in

subparts A through C of this part. In

addition, the following requirements

apply to MCANs submitted under this

subpart:

(a) When to submit a MCAN. A MCAN

must be submitted at least 90 calendar

days prior to manufacturing or

importing a new microorganism and at

least 90 calendar days prior to

manufacturing, importing, or processing

a microorganism for a significant new

use.

(b) Section 5(b) of the Act. The

submitter must comply with any

applicable requirement of section 5(b) of

the Act for the submission of test data.

(c) Contents of a MCAN. Each person

who submits a MCAN under this

subpart must provide the information

and test data described in §§ 725.155

and 725.160.

(d) Recordkeeping. Each person who

submits a MCAN under this subpart

must comply with the recordkeeping

requirements of § 725.65.

§ 725.155 Information to be included in the

MCAN.

(a) Each person who is required by

this part to submit a MCAN must

include the information specified in

paragraphs (c) through (h) of this

section, to the extent it is known to or

reasonably ascertainable by that person.

However, no person is required to

include information which relates solely

to exposure of humans or ecological

populations outside of the United

States.

(b) Each person should also submit, in

writing, all other information known to

or reasonably ascertainable by that

person that would permit EPA to make

a reasoned evaluation of the health and

environmental effects of the

microorganism, or any microbial

mixture or article, including

information on its effects on humans,

animals, plants, and other

microorganisms, and in the

environment. The information to be

submitted under this subpart includes

the information listed in paragraphs (c)

through (h) of this section relating to the

manufacture, processing, distribution in

commerce, use, and disposal of the new

microorganism.

(c) Submitter identification. (1) The

name and headquarters address of the

submitter.

(2) The name, address, and office

telephone number (including area code)

of the principal technical contact

representing the submitter.

(d) Microorganism identity

information. Persons must submit

sufficient information to allow the

microorganism to be accurately and

unambiguously identified for listing

purposes as required by § 725.12.

(1) Description of the recipient

microorganism and the new

microorganism. (i) Data substantiating

the taxonomy of the recipient

microorganism and the new

microorganism to the level of strain, as

appropriate. In lieu of data, EPA will

accept a letter from a culture collection

substantiating taxonomy, provided EPA,

upon request to the submitter, may have

access to the data supporting the

taxonomic designation.

(ii) Information on the morphological

and physiological features of the new

microorganism.

(iii) Other specific data by which the

new microorganism may be uniquely

identified for Inventory purposes.

(2) Genetic construction of the new

microorganism. (i) Data substantiating

the taxonomy of the donor organism(s).

In lieu of data, EPA will accept a letter

from a culture collection substantiating

taxonomy, provided EPA, upon request

to the submitter, may have access to the
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17945

data supporting the taxonomic

designation.

(ii) Description of the traits for which

the new microorganism has been

selected or developed and other traits

known to have been added or modified.

(iii) A detailed description of the

genetic construction of the new

microorganism, including the technique

used to modify the microorganism (e.g.,

fusion of cells, injection of DNA,

electroporation or chemical poration, or

methods used for induced mutation and

selection). The description should

include, for example, a description of

the introduced genetic material,

including any regulatory sequences and

structural genes and the products of

those genes; how the introduced genetic

material is expected to affect behavior of

the recipient; expression, alteration, and

stability of the introduced genetic

material; methods for vector

construction and introduction; and a

description of the regulatory and

structural genes that are components of

the introduced genetic material,

including genetic maps of the

introduced sequences.

(3) Phenotypic and ecological

characteristics. (i) Habitat, geographical

distribution, and source of the recipient

microorganism.

(ii) Survival and dissemination under

relevant environmental conditions

including a description of methods for

detecting the new or recipient

microorganism(s) in the environment

and the sensitivity limit of detection for

these techniques.

(iii) A description of anticipated

biological interactions with and effects

on target organisms and other organisms

such as competitors, prey, hosts,

symbionts, parasites, and pathogens; a

description of host range; a description

of pathogenicity, infectivity, toxicity,

virulence, or action as a vector of

pathogens; and capacity for genetic

transfer under laboratory and relevant

environmental conditions.

(iv) A description of anticipated

involvement in biogeochemical or

biological cycling processes,

involvement in rate limiting steps in

mineral or nutrient cycling, or

involvement in inorganic compounds

cycling (such as possible sequestration

or transformation of heavy metals).

(e) Byproducts. A description of the

byproducts resulting from the

manufacture, processing, use, and

disposal of the new microorganism.

(f) Total production volume. The

estimated maximum amount of the new

microorganism intended to be

manufactured or imported during the

first year of production and the

estimated maximum amount to be

manufactured or imported during any

consecutive 12–month period during

the first 3 years of production. This

estimate may be by weight or volume

and should include an estimation of

viability (i.e., viable cells per unit

volume or colony forming units per unit

dry weight).

(g) Use information. A description of

intended categories of use by function

and application, the estimated percent

of production volume devoted to each

category of use, and the percent of the

new microorganism in the formulation

for each commercial or consumer use.

(h) Worker exposure and

environmental release. (1) For sites

controlled by the submitter:

(i) The identity of sites where the new

microorganism will be manufactured,

processed, or used. For purposes of this

section, the site for a person who

imports a new microorganism is the site

of the operating unit within the person’s

organization which is directly

responsible for importing the new

microorganism and which controls the

import transaction. The import site may

in some cases be the organization’s

headquarters office in the United States.

(ii) A process description of each

manufacture, processing, and use

operation, which includes a diagram of

the major unit operations and

conversions, the identity and entry

point of all feedstocks, and the identity

of any possible points of release of the

new microorganism from the process,

including a description of all controls,

including engineering controls, used to

prevent such releases.

(iii) Worker exposure information,

including worker activities, physical

form of process streams which contain

the new microorganism to which

workers may be exposed, the number of

workers, and the duration of activities.

(iv) Information on release of the new

microorganism to the environment,

including the quantity and media of

release and type of control technology

used.

(v) A narrative description of the

intended transport of the new

microorganism, including the means of

transport, containment methods to be

used during transport, and emergency

containment procedures to be followed

in case of accidental release.

(vi) Procedures for disposal of any

articles, waste, clothing, or other

equipment involved in the activity,

including procedures for inactivation of

the new microorganism, containment,

disinfection, and disposal of

contaminated items.

(2) For sites not controlled by the

submitter, a description of each type of

processing and use operation involving

the new microorganism, including

identification of the estimated number

of processing or use sites, situations in

which worker exposure to and/or

environmental release of the new

microorganism will occur, the number

of workers exposed and the duration of

exposure; procedures for transport of

the new microorganism and for

disposal, including procedures for

inactivation of the new microorganism;

and control measures which limit

worker exposure and environmental

release.

§ 725.160 Submission of health and

environmental effects data.

(a) Test data on the new

microorganism in the possession or

control of the submitter. (1) Except as

provided in § 725.25(h), and in addition

to the information required by

§ 725.155(d)(3), each MCAN must

contain all test data in the submitter’s

possession or control which are related

to the effects on health or the

environment of any manufacture,

processing, distribution in commerce,

use, or disposal of the new

microorganism or any microbial mixture

or article containing the new

microorganism, or any combination of

such activities. This includes test data

concerning the new microorganism in a

pure culture or formulated form as used

or as intended to be used in one of the

activities listed above.

(2) A full report or standard literature

citation must be submitted for the

following types of test data:

(i) Health effects data.

(ii) Ecological effects data.

(iii) Physical and chemical properties

data.

(iv) Environmental fate

characteristics.

(v) Monitoring data and other test data

related to human exposure to or

environmental release of the new

microorganism.

(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
17946 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

and address of the laboratory

developing the data; progress to date;

types of data collected, significant

preliminary results; and anticipated

completion date.

(ii) If a test or experiment is

completed before the MCAN review

period ends, the person must submit the

study, report, or test, as specified in

paragraph (a)(3)(i) of this section, to the

address listed in § 725.25(c) within 10

days of receiving it, but no later than 5

days before the end of the review

period. If the test or experiment is

completed during the last 5 days of the

review period, the submitter must

immediately inform its EPA contact for

that submission by telephone.

(5) For test data in the submitter’s

possession or control which are not

listed in paragraph (a)(2) of this section,

a person is not required to submit a

complete report. The person must

submit a summary of the data. If EPA so

requests, the person must submit a full

report within 10 days of the request, but

no later than 5 days before the end of

the review period.

(6) All test data described under

paragraph (a) of this section are subject

to these requirements, regardless of their

age, quality, or results.

(b) Other data concerning the health

and environmental effects of the new

microorganism that are known to or

reasonably ascertainable by the

submitter. (1) Except as provided in

§ 725.25(h), and in addition to the

information required by § 725.155(c)(3),

any person who submits a MCAN must

describe the following data, including

any data from a health and safety study

of a microorganism, if the data are

related to effects on health or the

environment of any manufacture,

processing, distribution in commerce,

use, or disposal of the microorganism, of

any microbial mixture or article

containing the new microorganism, or of

any combination of such activities:

(i) Any data, other than test data, in

the submitter’s possession or control.

(ii) Any data, including test data,

which are not in the submitter’s

possession or control, but which are

known to or reasonably ascertainable by

the submitter. For the purposes of this

section, data are known to or reasonably

ascertainable by the submitter if the data

are known to any of its employees or

other agents who are associated with the

research and development, test

marketing, or commercial marketing of

the microorganism.

(2) Data that must be described

include data concerning the new

microorganism in a pure culture or

formulated form as used or as intended

to be used in one of the activities listed

in paragraph (b)(1) of this section.

(3) The description of data reported

under paragraph (b) of this section must

include:

(i) If the data appear in the open

scientific literature, a standard literature

citation, which includes the author,

title, periodical name, date of

publication, volume, and pages.

(ii) If the data are not available in the

open scientific literature, a description

of the type of data and summary of the

results, if available, and the names and

addresses of persons the submitter

believes may have possession or control

of the data.

(4) All data described in paragraph (b)

of this section are subject to these

requirements, regardless of their age,

quality, or results; and regardless of

whether they are complete at the time

the MCAN is submitted.

§ 725.170 EPA review of the MCAN.

General procedures for review of all

submissions under this part are

contained in §§ 725.28 through 725.60.

In addition, the following procedures

apply to EPA review of MCANs

submitted under this subpart:

(a) Length of the review period. The

MCAN review period specified in

section 5(a) of the Act runs for 90 days

from the date the Document Control

Officer for the Office of Pollution

Prevention and Toxics receives a

complete MCAN, or the date EPA

determines the MCAN is complete

under § 725.33, unless the Agency

extends the period under section 5(c) of

the Act and § 725.56.

(b) Notice of expiration of MCAN

review period. (1) EPA will notify the

submitter that the MCAN review period

has expired or that EPA has completed

its review of the MCAN. Expiration of

the review period does not constitute

EPA approval or certification of the new

microorganism, and does not mean that

EPA may not take regulatory action

against the microorganism in the future.

(2) After expiration of the MCAN

review period, in the absence of

regulatory action by EPA under section

5(e), 5(f), or 6(a) of the Act, the

submitter may manufacture or import

the microorganism even if the submitter

has not received notice of expiration.

(3) Early notification that EPA has

completed its review does not permit

commencement of manufacture or

import prior to the expiration of the 90–

day MCAN review period.

(c) No person submitting a MCAN in

response to the requirements of this

subpart may manufacture, import, or

process a microorganism subject to this

subpart until the review period,

including all extensions and

suspensions, has expired.

§ 725.190 Notice of commencement of

manufacture or import.

(a) Applicability. Any person who

commences the manufacture or import

of a new microorganism for nonexempt,

commercial purposes for which that

person previously submitted a section

5(a) notice under this part must submit

a notice of commencement (NOC) of

manufacture or import.

(b) When to report. (1) If manufacture

or import for nonexempt, commercial

purposes begins on or after May 27,

1997, the submitter must submit the

NOC to EPA no later than 30 calendar

days after the first day of such

manufacture or import.

(2) If manufacture or import for

nonexempt, commercial purposes began

or will begin before May 27, 1997, the

submitter must submit the NOC by May

27, 1997.

(3) Submission of an NOC prior to the

commencement of manufacture or

import is a violation of section 15 of the

Act.

(c) Information to be reported. The

NOC must contain the following

information: Specific microorganism

identity, MCAN number, and the date

when manufacture or import

commences. If the person claimed

microorganism identity confidential in

the MCAN, and wants the identity to be

listed on the confidential Inventory, the

claim must be reasserted and

resubstantiated in accordance with

§ 725.85(b). Otherwise, EPA will list the

specific microorganism identity on the

public Inventory.

(d) Where to submit. NOCs should be

submitted to the address listed in

§ 725.25(c).

Subpart E—Exemptions for Research and

Development Activities

§ 725.200 Scope and purpose.

(a) This subpart describes exemptions

from the reporting requirements under

subpart D of this part for research and

development activities involving

microorganisms.

(b) In lieu of complying with subpart

D of this part, persons described in

§ 725.205 may submit a TSCA

Experimental Release Application

(TERA) for research and development

activities involving microorganisms or

otherwise comply with this subpart.

(c) Exemptions from part 725 are

provided at §§ 725.232, 725.234, and

725.238.

(d) Submission requirements specific

for TERAs are described at § 725.250.

(e) Data requirements for TERAs are

set forth in §§ 725.255 and 725.260.
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17947

(f) EPA review procedures specific for

TERAs are set forth in §§ 725.270 and

725.288.

(g) Subparts A through C of this part

apply to any submission under this

subpart.

§ 725.205 Persons who may report under

this subpart.

(a) Commercial research and

development activities involving new

microorganisms or significant new uses

of microorganisms are subject to

reporting under this part unless they

qualify for an exemption under this

part.

(b) Commercial purposes for research

and development means that the

activities are conducted with the

purpose of obtaining an immediate or

eventual commercial advantage for the

researcher and would include:

(1) All research and development

activities which are funded directly, in

whole or in part, by a commercial entity

regardless of who is actually conducting

the research. Indications that the

research and development activities are

funded directly, in whole or in part,

may include, but are not limited to:

(i) Situations in which a commercial

entity contracts directly with a

university or researcher; or

(ii) Situations in which a commercial

entity gives a conditional grant where

the commercial entity holds patent

rights, or establishes a joint venture

where the commercial entity holds

patent or licensing rights; or

(iii) Any other situation in which the

commercial entity intends to obtain an

immediate or eventual commercial

advantage for the commercial entity

and/or the researcher.

(2) Research and development

activities that are not funded directly by

a commercial entity, if the researcher

intends to obtain an immediate or

eventual commercial advantage.

Indications that the researcher intends

to obtain an immediate or eventual

commercial advantage may include, but

are not limited to:

(i) The research is directed toward

developing a commercially viable

improvement of a product already on

the market; or

(ii) The researcher has sought or is

seeking commercial funding for the

purpose of developing a commercial

application; or

(iii) The researcher or university has

sought or is seeking a patent to protect

a commercial application which the

research is developing; or

(iv) Other evidence that the researcher

is aware of a commercial application for

the research and has directed the

research toward developing that

application.

(c) Certain research and development

activities involving microorganisms

subject to jurisdiction under the Act are

exempt from reporting under this part.

A person conducting research and

development activities which meet the

conditions for the exemptions described

in §§ 725.232, 725.234, or 725.238 is

exempt from TERA reporting under this

subpart.

(d) A microorganism is not exempt

from reporting under subpart D of this

part if any amount of the

microorganism, including as part of a

mixture, is processed, distributed in

commerce, or used, for any commercial

purpose other than research and

development.

(e) Quantities of the inactivated

microorganism, or mixtures or articles

containing the inactivated

microorganism, remaining after

completion of research and

development activities may be disposed

of as a waste in accordance with

applicable Federal, State, and local

regulations.

(f) A person who manufactures,

imports, or processes a microorganism

solely for research and development is

not required to comply with the

requirements of this section if:

(1) The person is manufacturing a

microbial pesticide identified in

§ 172.45(c), or

(2) The person is manufacturing a

microbial pesticide for which an

Experimental Use Permit is required,

pursuant to § 172.3; or

(3) The person is manufacturing a

microbial pesticide for which a

notification or an Experimental Use

Permit is not required to be submitted.

§ 725.232 Activities subject to the

jurisdiction of other Federal programs or

agencies.

This part does not apply to any

research and development activity that

meets all of the following conditions.

(a) The microorganism is

manufactured, imported, or processed

solely for research and development

activities.

(b) There is no intentional testing of

a microorganism outside of a structure,

as structure is defined in § 725.3.

(c)(1) The person receives research

funds from another Federal agency, and

the funds are awarded on the condition

that the research will be conducted in

accordance with the relevant portions of

the NIH Guidelines, or

(2) A Federal agency or program

otherwise imposes the legally binding

requirement that the research is to be

conducted in accordance with relevant

portions of the NIH Guidelines.

§ 725.234 Activities conducted inside a

structure.

A person who manufactures, imports,

or processes a microorganism is not

subject to the reporting requirements

under subpart D of this part if all of the

following conditions are met:

(a) The microorganism is

manufactured, imported, or processed

solely for research and development

activities.

(b) The microorganism is used by, or

directly under the supervision of, a

technically qualified individual, as

defined in § 725.3. The technically

qualified individual must maintain

documentation of the procedures

selected to comply with paragraph (d) of

this section and must ensure that the

procedures are used.

(c) There is no intentional testing of

a microorganism outside of a structure,

as structure is defined in § 725.3.

(d) Containment and/or inactivation

controls. (1) Selection and use of

containment and/or inactivation

controls inside a structure for a

particular microorganism shall take into

account the following:

(i) Factors relevant to the organism’s

ability to survive in the environment.

(ii) Potential routes of release in air,

solids and liquids; in or on waste

materials and equipment; in or on

people, including maintenance and

custodial personnel; and in or on other

organisms, such as insects and rodents.

(iii) Procedures for transfer of

materials between facilities.

(2) The technically qualified

individual’s selection of containment

and/or inactivation controls shall be

approved and certified by an authorized

official (other than the TQI) of the

institution that is conducting the test

prior to the commencement of the test.

(3) Records shall be developed and

maintained describing the selection and

use of containment and/or inactivation

controls, as specified in § 725.235(c).

These records, which must be

maintained at the location where the

research and development activity is

being conducted, shall be submitted to

EPA upon written request and within

the time frame specified in EPA’s

request.

(4) Subsequent to EPA review of

records in accordance with paragraph

(d)(3) of this section, changes to the

containment/inactivation controls

selected under paragraph (d)(1) of this

section must be made upon EPA order.

Failure to comply with EPA’s order

shall result in automatic loss of

eligibility for an exemption under this

section.

(e) The manufacturer, importer, or

processor notifies all persons in its
17948 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

employ or to whom it directly

distributes the microorganism, who are

engaged in experimentation, research, or

analysis on the microorganism,

including the manufacture, processing,

use, transport, storage, and disposal of

the microorganism associated with

research and development activities, of

any risk to health, identified under

§ 725.235(a), which may be associated

with the microorganism. The

notification must be made in accordance

with § 725.235(b).

§ 725.235 Conditions of exemption for

activities conducted inside a structure.

(a) Determination of risks. To

determine whether notification under

§ 725.234(e) is required, the

manufacturer, importer, or processor

must do one of the following:

(1) For research conducted in

accordance with the NIH Guidelines,

the manufacturer, importer, or processor

must meet the conditions laid out at IVB-4-d of the NIH Guidelines; or

(2) For all other research conducted in

accordance with § 725.234, the

manufacturer, importer, or processor

must review and evaluate the following

information to determine whether there

is reason to believe there is any risk to

health which may be associated with

the microorganism:

(i) Information in its possession or

control concerning any significant

adverse reaction of persons exposed to

the microorganism which may

reasonably be associated with such

exposure.

(ii) Information provided to the

manufacturer, importer, or processor by

a supplier or any other person

concerning a health risk believed to be

associated with the microorganism.

(iii) Health and environmental effects

data in its possession or control

concerning the microorganism.

(iv) Information on health effects

which accompanies any EPA rule or

order issued under TSCA section 4, 5,

or 6 of the Act that applies to the

microorganism and of which the

manufacturer, importer, or processor

has knowledge.

(b) Notification to employees and

others. (1) The manufacturer, importer,

or processor must notify the persons

identified in § 725.234(e) by means of a

container labeling system, conspicuous

placement of notices in areas where

exposure may occur, written

notification to each person potentially

exposed, or any other method of

notification which adequately informs

persons of health risks which the

manufacturer, importer, or processor

has reason to believe may be associated

with the microorganism, as determined

under paragraph (a) of this section.

(2) If the manufacturer, importer, or

processor distributes a microorganism

manufactured, imported, or processed

under this section to persons not in its

employ, the manufacturer, importer, or

processor must in written form:

(i) Notify those persons that the

microorganism is to be used only for

research and development purposes and

the requirements of § 725.234 are to be

met.

(ii) Provide the notice of health risks

specified in paragraph (b)(1) of this

section.

(3) The adequacy of any notification

under this section is the responsibility

of the manufacturer, importer, or

processor.

(c) Recordkeeping. (1) For research

conducted in accordance with the NIH

Guidelines, a person who manufactures,

imports, or processes a microorganism

under this section must retain the

following records:

(i) Documentation that the NIH

Guidelines have been adhered to. Such

documentation shall include:

(A) For experiments subject to

Institutional Biosafety Committee

review, or notification simultaneous

with initiation of the experiment, the

information submitted for review or

notification, along with standard

laboratory records, shall satisfy the

recordkeeping requirements specified in

§ 725.234(d)(3).

(B) For experiments exempt from

Institutional Biosafety Committee

review or notification simultaneous

with initiation of the experiment,

documentation of the exemption, along

with standard laboratory records, shall

satisfy the recordkeeping requirement

specified in § 725.234(d)(3).

(ii) Documentation of how the

following requirements are satisfied

under the NIH Guidelines:

(A) Copies or citations to information

reviewed and evaluated to determine

the need to make any notification of

risk.

(B) Documentation of the nature and

method of notification of risk, including

copies of any labels or written notices

used.

(C) The names and addresses of any

persons other than the manufacturer,

importer, or processor to whom the

substance is distributed, the identity of

the microorganism, the amount

distributed, and copies of the

notifications required.

(2) For all other research conducted in

accordance with § 725.234, a person

who manufacturers, imports, or

processes a microorganism under this

section, must maintain the following

records:

(i) Records describing selection and

use of containment and/or inactivation

controls required by § 725.234(d)(3) and

certification by an authorized official

required by § 725.234(d)(2) for each

microorganism.

(ii) Copies or citations to information

reviewed and evaluated under

paragraph (a) of this section to

determine the need to make any

notification of risk.

(iii) Documentation of the nature and

method of notification under paragraph

(b)(1) of this section, including copies of

any labels or written notices used.

(iv) The names and addresses of any

persons other than the manufacturer,

importer, or processor to whom the

substance is distributed, the identity of

the microorganism, the amount

distributed, and copies of the

notifications required under paragraph

(b)(2) of this section.

§ 725.238 Activities conducted outside a

structure.

(a) Exemption. (1) Research and

development activities involving

intentional testing in the environment of

certain microorganisms listed in

§ 725.239 may be conducted without

prior review by EPA if all of the

conditions of this section and § 725.239

are met.

(2) The research and development

activity involving a microorganism

listed in § 725.239 must be conducted

by, or directly under the supervision of,

a technically qualified individual, as

defined in § 725.3.

(b) Certification. To be eligible for the

exemption under this section, a

manufacturer or importer must submit

to EPA prior to initiation of the activity

a document signed by an authorized

official containing the following

information:

(1) Name, address, and telephone

number of the manufacturer or importer.

(2) Location, estimated duration, and

planned start date of the test.

(3) Certification of the following:

(i) Compliance with the conditions of

the exemption specified for the

microorganism in § 725.239.

(ii) If state and/or local authorities

have been notified of the activity,

evidence of notification.

(c) Recordkeeping. Persons who

conduct research and development

activities under this section must

comply with the recordkeeping

requirements of § 725.65 and retain

documentation that supports their

compliance with the requirements of

this section and the specific

requirements for the microorganism

listed in § 725.239.
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17949

§ 725.239 Use of specific microorganisms

in activities conducted outside a structure.

(a) Bradyrhizobium japonicum. To

qualify for an exemption under this

section, all of the following conditions

must be met for a test involving

Bradyrhizobium japonicum:

(1) Characteristics of recipient

microorganism. The recipient

microorganism is limited to strains of

Bradyrhizobium japonicum.

(2) Modification of traits. (i) The

introduced genetic material must meet

the criteria for poorly mobilizable listed

in § 725.421(c).

(ii) The introduced genetic material

must consist only of the following

components:

(A) The structural gene(s) of interest,

which have the following limitations:

(1) For structural genes encoding

marker sequences, the gene is limited to

the aadH gene, which confers resistance

to the antibiotics streptomycin and

spectinomycin.

(2) For traits other than antibiotic

resistance, the structural gene must be

limited to the genera Bradyrhizobium

and Rhizobium.

(B) The regulatory sequences

permitting the expression of solely the

gene(s) of interest.

(C) Associated nucleotide sequences

needed to move genetic material,

including linkers, homopolymers,

adaptors, transposons, insertion

sequences, and restriction enzyme sites.

(D) The vector nucleotide sequences

needed for vector transfer.

(E) The vector nucleotide sequences

needed for vector maintenance.

(3) Limitations on exposure. (i) The

test site area must be no more than 10

terrestrial acres.

(ii) The technically qualified

individual must select appropriate

methods to limit the dissemination of

modified Bradyrhizobium japonicum.

(b) Rhizobium meliloti. To qualify for

an exemption under this section, all of

the following conditions must be met

for a test involving Rhizobium meliloti:

(1) Characteristics of recipient

microorganism. The recipient

microorganism is limited to strains of

Rhizobium meliloti.

(2) Modification of traits. (i) The

introduced genetic material must meet

the criteria for poorly mobilizable listed

in § 725.421(c) of this part.

(ii) The introduced genetic material

must consist only of the following

components:

(A) The structural gene(s) of interest,

which have the following limitations:

(1) For structural genes encoding

marker sequences, the gene is limited to

the aadH gene, which confers resistance

to the antibiotics streptomycin and

spectinomycin.

(2) For traits other than antibiotic

resistance, the structural gene must be

limited to the genera Bradyrhizobium

and Rhizobium.

(B) The regulatory sequences

permitting the expression of solely the

gene(s) of interest.

(C) Associated nucleotide sequences

needed to move genetic material,

including linkers, homopolymers,

adaptors, transposons, insertion

sequences, and restriction enzyme sites.

(D) The vector nucleotide sequences

needed for vector transfer.

(E) The vector nucleotide sequences

needed for vector maintenance.

(3) Limitations on exposure. (i) The

test site area must be no more than 10

terrestrial acres.

(ii) The technically qualified

individual must select appropriate

methods to limit the dissemination of

modified Rhizobium meliloti.

§ 725.250 Procedural requirements for the

TERA.

General requirements for all

submissions under this part are

contained in subparts A through C of

this part. In addition, the following

requirements apply to TERAs submitted

under this subpart:

(a) When to submit the TERA. Each

person who is eligible to submit a TERA

under this subpart must submit the

TERA at least 60 calendar days before

the person intends to initiate the

proposed research and development

activity.

(b) Contents of the TERA. Each person

who submits a TERA under this subpart

must provide the information and test

data described in §§ 725.255 and

725.260. In addition, the submitter must

supply sufficient information to enable

EPA to evaluate the effects of all

activities for which approval is

requested.

(c) A person may submit a TERA for

one or more microorganisms and one or

more research and development

activities, including a research program.

(d) EPA will either approve the TERA,

with or without conditions, or

disapprove it under procedures

established in this subpart.

(e) The manufacturer, importer, or

processor who receives a TERA

approval must comply with all terms of

the approval, as well as conditions

described in the TERA, and remains

liable for compliance with all terms and

conditions, regardless of who conducts

the research and development activity.

Any person conducting the research and

development activity approved under

the TERA must comply with all terms

of the TERA approval, as well as the

conditions described in the TERA.

(f) Recordkeeping. Persons submitting

a TERA must comply with the

recordkeeping requirements of § 725.65.

In addition, the following requirements

apply to TERAs:

(1) Each person submitting a TERA

under this part must retain

documentation of information contained

in the TERA for a period of 3 years from

the date that the results of the study are

submitted to the Agency.

(2) Summaries of all data,

conclusions, and reports resulting from

the conduct of the research and

development activity under the TERA

must be submitted to the EPA address

identified in § 725.25(c) within 1 year of

the termination of the activity.

§ 725.255 Information to be included in the

TERA.

(a) To review a TERA, EPA must have

sufficient information to permit a

reasoned evaluation of the health and

environmental effects of the planned

test in the environment. The person

seeking EPA approval must submit all

information known to or reasonably

ascertainable by the submitter on the

microorganism(s) and the research and

development activity, including

information not listed in paragraphs (c),

(d), and (e) of this section that the

person believes will be useful for EPA’s

risk assessment. The TERA must be in

writing and must include at least the

information described in the following

paragraphs.

(b) When specific information is not

submitted, an explanation of why such

information is not available or not

applicable must be included.

(c) Persons applying for a TERA, must

include the submitter identification and

microorganism identity information

required for MCANs in § 725.155(c),

(d)(1), and (d)(2).

(d) Persons applying for a TERA must

submit phenotypic and ecological

characteristics information required in

§ 725.155(d)(3) as it relates directly to

the conditions of the proposed research

and development activity.

(e) Persons applying for a TERA must

also submit the following information

about the proposed research and

development activity:

(1) A detailed description of the

proposed research and development

activity. (i) The objectives and

significance of the activity and a

rationale for testing the microorganisms

in the environment.

(ii) Number of microorganisms

released (including viability per volume

if applicable) and the method(s) of

application or release.

(iii) Characteristics of the test site(s),

including location, geographical,
17950 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

physical, chemical, and biological

features, proximity to human habitation

or activity, and description of site

characteristics that would influence

dispersal or confinement.

(iv) Target organisms (if the

microorganism(s) to be tested has an

intended target), including

identification of each target organism

and anticipated mechanism and result

of interaction.

(v) Planned start date and duration of

each activity.

(vi) If State and/or local authorities

have been notified of the activity,

evidence of notification.

(2) Information on monitoring,

confinement, mitigation, and emergency

termination procedures. (i) Confinement

procedures for the activity, access and

security measures, and procedures for

routine termination of the activity.

(ii) Mitigation and emergency

procedures.

(iii) Measures to detect and control

potential adverse effects.

(iv) Name of principal investigator

and chief of site personnel responsible

for emergency procedures.

(v) Personal protective equipment,

engineering controls, and procedures to

be followed to minimize dispersion of

the microorganism(s) by people,

machinery, or equipment.

(vi) Procedures for disposal of any

articles, waste, clothing, machinery, or

other equipment involved in the

experimental release, including

methods for inactivation of the

microorganism(s), containment,

disinfection, and disposal of

contaminated items.

§ 725.260 Submission of health and

environmental effects data.

Each TERA must contain all available

data concerning actual or potential

effects on health or the environment of

the new microorganism that are in the

possession or control of the submitter

and a description of other data known

to or reasonably ascertainable by the

submitter that will permit a reasoned

evaluation of the planned test in the

environment. The data must be reported

in the manner described in

§ 725.160(a)(3) and (b)(3).

§ 725.270 EPA review of the TERA.

General procedures for review of all

submissions under this part are

contained in §§ 725.28 through 725.60.

In addition, the following procedures

apply to EPA review of applications

submitted under this subpart:

(a) Length of the review period. (1)

The review period for the TERA will be

60 days from the date the Document

Control Officer for the Office of

Pollution Prevention and Toxics

receives a complete TERA, or the date

EPA determines the TERA is complete

under § 725.33, unless EPA finds good

cause for an extension under § 725.56.

(2) A submitter shall not proceed with

the research and development activity

described in the TERA unless and until

EPA provides written approval of the

TERA. A submitter may receive early

approval if a review is completed in less

than 60 days.

(b) EPA decision regarding proposed

TERA activity. (1) A decision

concerning a TERA under this subpart

will be made by the Administrator, or a

designee.

(2) If EPA determines that the

proposed research and development

activity for the microorganism does not

present an unreasonable risk of injury to

health or the environment, EPA will

notify the submitter that the TERA is

approved and that the submitter can

proceed with the proposed research and

development activity described in the

TERA.

(3) EPA may include requirements

and conditions in its approval of the

TERA that would be stated in the TERA

approval under paragraph (c) of this

section.

(4) If EPA concludes that it cannot

determine that the proposed research

and development activity described in

the TERA will not present an

unreasonable risk of injury to health or

the environment, EPA will deny the

TERA and will provide reasons for the

denial in writing.

(c) TERA approval. (1) A TERA

approval issued by EPA under this

section is legally binding on the TERA

submitter.

(2) When EPA approves a TERA, the

submitter must conduct the research

and development activity only as

described in the TERA and in

accordance with any requirements and

conditions prescribed by EPA in its

approval of the TERA.

(3) Any person who fails to conduct

the research and development activity

as described in the TERA and in

accordance with any requirements and

conditions prescribed by EPA in its

approval of the TERA under this

section, shall be in violation of sections

5 and 15 of the Act and be subject to

civil and criminal penalties under

section 16 of the Act.

§ 725.288 Revocation or modification of

TERA approval.

(a) Significant questions about risk.

(1) If, after approval of a TERA under

this subpart, EPA receives information

which raises significant questions about

EPA’s determination that the activity

does not present an unreasonable risk of

injury to health or the environment,

EPA will notify the submitter in writing

of those questions.

(2) The submitter may, within 10 days

of receipt of EPA’s notice, provide in

writing additional information or

arguments concerning the significance

of the questions and whether EPA

should modify or revoke the approval of

the TERA.

(3) After considering any such

information and arguments, EPA will

decide whether to change its

determination regarding approval of the

TERA.

(i) If EPA determines that the activity

will not present an unreasonable risk of

injury to health or the environment, it

will notify the submitter in writing. To

make this finding, EPA may prescribe

additional conditions which must be

followed by the submitter.

(ii) If EPA determines that it can no

longer conclude that the activity will

not present an unreasonable risk of

injury to health or the environment, it

will notify the submitter in writing that

EPA is revoking its approval and state

its reasons. In that event, the submitter

must terminate the research and

development activity within 48 hours of

receipt of the notice in accordance with

directions provided by EPA in the

notice.

(b) Evidence of unreasonable risk. (1)

If, after approval of a TERA under this

subpart, EPA determines that the

proposed research and development

activity will present an unreasonable

risk of injury to health or the

environment, EPA will notify the

submitter in writing and state its

reasons.

(2) In the notice, EPA may prescribe

additional safeguards to address or

reduce the risk, or may instruct the

submitter to suspend the research and

development activities.

(3) Within 48 hours, the submitter

must implement the instructions

contained in the notice. The submitter

may then submit additional information

or arguments concerning the matters

raised by EPA and whether EPA should

modify or revoke the approval of the

TERA in accordance with paragraph

(a)(2) of this section.

(4) EPA will consider the information

and arguments in accordance with

paragraph (a)(3) of this section.

(5) Following consideration of the

information and arguments under

paragraph (a)(3) of this section, if EPA

notifies the submitter that the R&D

activity must be suspended or

terminted, the submitter may resume

the activity only upon written notice

from EPA that EPA has approved
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17951

resumption of the activity. In approving

resumption of an activity, EPA may

prescribe additional conditions which

must be followed by the submitter.

(c) Modifications. If, after approval of

a TERA under this subpart, the

submitter concludes that it is necessary

to alter the conduct of the research and

development activity in a manner which

would result in the activity being

different from that described in the

TERA agreement and any conditions

EPA prescribed in its approval, the

submitter must inform the EPA contact

for the TERA and may not modify the

activity without the approval of EPA.

Subpart F—Exemptions for Test Marketing

§ 725.300 Scope and purpose.

(a) This subpart describes exemptions

from the reporting requirements under

subpart D of this part for test marketing

activities involving microorganisms.

(b) In lieu of complying with subpart

D of this part, persons described in

§ 725.305 may submit an application for

a test marketing exemption (TME).

(c) Submission requirements specific

for TME applications are described at

§ 725.350.

(d) Data requirements for TME

applications are set forth in § 725.355.

(e) EPA review procedures specific for

TMEs are set forth in § 725.370.

(f) Subparts A through C of this part

apply to any submission under this

subpart.

§ 725.305 Persons who may apply under

this subpart.

A person identified in this section

may apply for a test marketing

exemption. EPA may grant the

exemption if the person demonstrates

that the microorganism will not present

an unreasonable risk of injury to health

or the environment as a result of the test

marketing. A person may apply under

this subpart for the following test

marketing activities:

(a) A person who intends to

manufacture or import for commercial

purposes a new microorganism.

(b) A person who intends to

manufacture, import, or process for

commercial purposes a microorganism

identified in subpart M of this part for

a significant new use.

§ 725.350 Procedural requirements for this

subpart.

General requirements for all

submissions under this part are

contained in subparts A through C of

this part. In addition, the following

requirements apply to applications

submitted under this subpart:

(a) Prenotice consultation. EPA

strongly suggests that for a TME, the

applicant contact EPA for a prenotice

consultation regarding eligibility for a

TME.

(b) When to submit a TME

application. Each person who is eligible

to apply for a TME under this subpart

must submit the application at least 45

calendar days before the person intends

to commence the test marketing activity.

(c) Recordkeeping. Each person who

is granted a TME must comply with the

recordkeeping requirements of § 725.65.

In addition, any person who obtains a

TME must retain documentation of

compliance with any restrictions

imposed by EPA when it grants the

TME. This information must be retained

for 3 years from the final date of

manufacture or import under the

exemption.

§ 725.355 Information to be included in the

TME application.

(a) To review a TME application, EPA

must have sufficient information to

permit a reasoned evaluation of the

health and environmental effects of the

planned test marketing activity. The

person seeking EPA approval must

submit all information known to or

reasonably ascertainable by the person

on the microorganism and the test

marketing activity, including

information not listed in paragraphs (c),

(d), and (e) of this section that the

person believes will demonstrate that

the microorganism will not present an

unreasonable risk of injury to health or

the environment as a result of the test

marketing. The TME application must

be in writing and must include at least

the information described in paragraphs

(b), (c), (d), and (e) of this section.

(b) When specific information is not

submitted, an explanation of why such

information is not available or not

applicable must be included.

(c) Persons applying for a TME must

submit the submitter identification and

microorganism identity information

required for MCANs in § 725.155(c),

(d)(1), and (d)(2).

(d) Persons applying for a TME must

submit phenotypic and ecological

characteristics information required in

§ 725.155(d)(3) as it relates directly to

the conditions of the proposed test

marketing activity.

(e) Persons applying for a TME must

also submit the following information

about the proposed test marketing

activity:

(1) Proposed test marketing activity.

(i) The maximum quantity of the

microorganism which the applicant will

manufacture or import for test

marketing.

(ii) The maximum number of persons

who may be provided the

microorganism during test marketing.

(iii) The maximum number of persons

who may be exposed to the

microorganism as a result of test

marketing, including information

regarding duration and route of such

exposures.

(iv) A description of the test

marketing activity, including its

duration and how it can be

distinguished from full-scale

commercial production and research

and development activities.

(2) Health and environmental effects

data. All existing data regarding health

and environmental effects of the

microorganism must be reported in

accordance with § 725.160.

§ 725.370 EPA review of the TME

application.

General procedures for review of all

submissions under this part are

contained in §§ 725.28 through 725.60.

In addition, the following procedures

apply to EPA review of TME

applications submitted under this

subpart:

(a) No later than 45 days after EPA

receives a TME, the Agency will either

approve or deny the application.

(b) A submitter may only proceed

with test marketing activities after

receipt of EPA approval.

(c) In approving a TME application,

EPA may impose any restrictions

necessary to ensure that the

microorganism will not present an

unreasonable risk of injury to health and

the environment as a result of test

marketing.

Subpart G—General Exemptions for New

Microorganisms

§ 725.400 Scope and purpose.

(a) This subpart describes exemptions

from reporting under subpart D of this

part, and from review under this part

altogether, for manufacturing and

importing of certain new

microorganisms for commercial

purposes.

(b) Recipient microorganisms eligible

for the tiered exemption from review

under this part are listed in § 725.420.

(c) Criteria for the introduced genetic

material contained in the new

microorganisms are described in

§ 725.421.

(d) Physical containment and control

technologies are described in § 725.422.

(e) The conditions for the Tier I

exemption are listed in § 725.424.

(f) In lieu of complying with subpart

D of this part, persons using recipient

microorganisms eligible for the tiered

exemption may submit a Tier II
17952 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

exemption request. The limited

reporting requirements for the Tier II

exemption, including data

requirements, are described in

§§ 725.450 and 725.455.

(g) EPA review procedures for the Tier

II exemption are set forth in § 725.470.

(h) Subparts A through C of this part

apply to any submission under this

subpart.

§ 725.420 Recipient microorganisms.

The following recipient

microorganisms are eligible for either

exemption under this subpart:

(a) Acetobacter aceti.

(b) Aspergillus niger.

(c) Aspergillus oryzae.

(d) Bacillus licheniformis.

(e) Bacillus subtilis.

(f) Clostridium acetobutylicum.

(g) Escherichia coli K-12.

(h) Penicillium roqueforti.

(i) Saccharomyces cerevisiae.

(j) Saccharomyces uvarum.

§ 725.421 Introduced genetic material.

For a new microorganism to qualify

for either exemption under this subpart,

introduced genetic material must meet

all of the criteria listed in this section.

(a) Limited in size. The introduced

genetic material must consist only of the

following:

(1) The structural gene(s) of interest.

(2) The regulatory sequences

permitting the expression of solely the

gene(s) of interest.

(3) Associated nucleotide sequences

needed to move genetic material,

including linkers, homopolymers,

adaptors, transposons, insertion

sequences, and restriction enzyme sites.

(4) The nucleotide sequences needed

for vector transfer.

(5) The nucleotide sequences needed

for vector maintenance.

(b) Well-characterized. For introduced

genetic material, well-characterized

means that the following have been

determined:

(1) The function of all of the products

expressed from the structural gene(s).

(2) The function of sequences that

participate in the regulation of

expression of the structural gene(s).

(3) The presence or absence of

associated nucleotide sequences and

their associated functions, where

associated nucleotide sequences are

those sequences needed to move genetic

material including linkers,

homopolymers, adaptors, transposons,

insertion sequences, and restriction

enzyme sites.

(c) Poorly mobilizable. The ability of

the introduced genetic material to be

transferred and mobilized is inactivated,

with a resulting frequency of transfer of

less than 10-8 transfer events per

recipient.

(d) Free of certain sequences. (1) The

introduced genetic material must not

contain a functional portion of any of

the toxin-encoding sequences described

in this paragraph (d).

(i) For the purposes of this section, a

functional portion of a toxin-encoding

sequence means any sequence which

codes for a polypeptide that has one of

the following effects:

(A) It directly or indirectly contributes

to toxic effects in humans. Directly

contributes to toxic effects in humans

means those sequences encoding

polypeptides that have direct toxicity to

target cells. An example of a sequence

which directly contributes to toxic

effects in humans is one which encodes

the portion of diphtheria toxin, listed in

paragraph (d)(2) of this section, capable

of interacting with elongation factor 2,

leading to inhibition of protein

synthesis in target respiratory, heart,

kidney, and nerve tissues. Indirectly

contributes to toxic effects in humans

means a sequence whose encoded

polypeptide is not directly toxic to

target cells, yet still adversely affects

humans. An example of a sequence

which indirectly contributes to toxic

effects is the sequence which encodes

the portion of the botulinum toxin,

listed in paragraph (d)(3) of this section,

capable of blocking the release of

acetylcholine from gangliosides.

Botulinum toxin affects neuromuscular

junctions by its blockage of

acetylcholine release, leading to

irreversible relaxation of muscles and

respiratory arrest.

(B) It binds a toxin or toxin precursor

to target human cells.

(C) It facilitates intracellular transport

of a toxin in target human cells.

(ii) While these toxins are listed (with

synonyms in parentheses) in paragraphs

(d)(2) through (d)(7) of this section

according to the source organism, it is

use of the nucleotide sequences that

encode the toxins that is being restricted

and not the use of the source organisms.

The source organisms are listed to

provide specificity in identification of

sequences whose use is restricted.

Although similar or identical sequences

may be isolated from organisms other

than those listed below in paragraphs

(d)(2) through (d)(7) of this section,

these comparable toxin sequences,

regardless of the organism from which

they are derived, must not be included

in the introduced genetic material.

(2) Sequences for protein synthesis

inhibitor.

Sequence Source Toxin Name

Corynebacterium

diphtheriae & C.

ulcerans

Diphtheria toxin

Pseudomonas

aeruginosa

Exotoxin A

Shigella dysenteriae Shigella toxin (Shiga

toxin, Shigella

dysenteriae type I

toxin, Vero cell

toxin)

Abrus precatorius,

seeds

Abrin

Ricinus communis,

seeds

Ricin

(3) Sequences for neurotoxins.

Sequence Source Toxin Name

Clostridium botulinum Neurotoxins A, B, C1,

D, E, F, G

(Botulinum toxins,

botulinal toxins)

Clostridium tetani Tetanus toxin

(tetanospasmin)

Proteus mirabilis Neurotoxin

Staphylococcus

aureus

Alpha toxin (alpha

lysin)

Yersinia pestis Murine toxin

Snake toxins

Bungarus caeruleus Caeruleotoxin

Bungarus multicinctus Beta-bungarotoxin

(phospholipase)

Crotalus spp. Crotoxin

(phospholipase)

Dendroaspis viridis Neurotoxin

Naja naja varieties Neurotoxin

Notechia scutatus Notexin

(phospholipase)

Oxyuranus scutellatus Taipoxin

Invertebrate toxins

Chironex fleckeri Neurotoxin

Androctnus australis Neurotoxin

Centruroides

sculpturatus

Neurotoxin

(4) Sequences for oxygen labile

cytolysins.

Sequence Source Toxin Name

Bacillus alve Alveolysin

Bacillus cereus Cereolysin

Bacillus laterosporus Laterosporolysin

Bacillus thuringiensis Thuringiolysin

Clostridium

bifermentans

Lysin

Clostridium botulinum Lysin

Clostridium caproicum Lysin

Clostridium chauvoei Delta-toxin

Clostridium

histolyticum

Epsilon-toxin

Clostridium novyi Gamma-toxin

Clostridium

oedematiens

Delta-toxin
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17953

Sequence Source Toxin Name

Clostridium

perfringens

Theta-toxin

(Perfringolysin)

Clostridium septicum Delta-toxin

Clostridium sordellii Lysin

Clostridium tetani Tetanolysin

Listeria

monocytogenes

Listeriolysin (A B)

Streptococcus

pneumoniae

Pneumolysin

Streptococcus

pyogene

Streptolysin O (SLO)

(5) Sequences for toxins affecting

membrane function.

Sequence Source Toxin Name

Bacillus anthracis Edema factor (Factors I II); Lethal factor (Factors II III)

Bacillus cereus Enterotoxin

(diarrheagenic

toxin, mouse lethal

factor)

Bordetella pertussis Adenylate cyclase

(Heat-labile factor);

Pertussigen (pertussis toxin, islet

activating factor,

histamine sensitizing factor,

lymphocytosis promoting factor)

Clostridium botulinum C2 toxin

Clostridium difficile Enterotoxin (toxin A)

Clostridium

perfringens

Beta-toxin; Deltatoxin

Escherichia coli &

other

Enterobacteriaceae

spp.

Heat-labile

enterotoxins (LT);

Heat-stable

enterotoxins (STa,

ST1 subtypes

ST1a ST1b; also

STb, STII)

Legionella

pneumophila

Cytolysin

Vibrio cholerae &

Vibrio mimicus

Cholera toxin

(choleragen)

(6) Sequences that affect membrane

integrity.

Sequence Source Toxin Name

Clostridium

bifermentans &

other Clostridium

spp

Lecithinase

Clostridium

perfringens

Alpha-toxin

(phospholipase C,

lecithinase);

Enterotoxin

Corynebacterium

pyogenes & other

Corynebacterium

spp.

Cytolysin

(phospholipase C),

Ovis toxin

(sphingomyelinase

D)

Sequence Source Toxin Name

Staphylococcus

aureus

Beta-lysin (beta toxin)

(7) Sequences that are general

cytotoxins.

Sequence Source Toxin Name

Adenia digitata Modeccin

Aeromonas

hydrophila

Aerolysin (beta-lysin,

cytotoxic lysin)

Clostridium difficile Cytotoxin (toxin B)

Clostridium

perfringens

Beta-toxin; Epsilontoxin; Kappa-toxin

Escherichia coli &

other

Enterobacteriaceae

spp.

Cytotoxin (Shiga-like

toxin, Vero cell

toxin)

Pseudomonas

aeruginosa

Proteases

Staphylococcus

aureus

Gamma lysin

(Gamma toxin);

Enterotoxins (SEA,

SEB, SEC, SED

SEE); Pyrogenic

exotoxins A B;

Toxic shock syndrome toxins

(TSST-1)

Staphylococcus

aureus &

Pseudomonas

aeruginosa

Leucocidin

(leukocidin,

cytotoxin)

Streptococcus

pyogenes

Streptolysin S (SLS);

Erythrogenic toxins

(scarlet fever toxins, pyrogenic

exotoxins)

Yersinia enterocolitica Heat-stable

enterotoxins (ST)

§ 725.422 Physical containment and

control technologies.

The manufacturer must meet all of the

following criteria for physical

containment and control technologies

for any facility in which the new

microorganism will be used for a Tier I

exemption; these criteria also serve as

guidance for a Tier II exemption.

(a) Use a structure that is designed

and operated to contain the new

microorganism.

(b) Control access to the structure.

(c) Provide written, published, and

implemented procedures for the safety

of personnel and control of hygiene.

(d) Use inactivation procedures

demonstrated and documented to be

effective against the new microorganism

contained in liquid and solid wastes

prior to disposal of the wastes. The

inactivation procedures must reduce

viable microbial populations by at least

6 logs in liquid and solid wastes.

(e) Use features known to be effective

in minimizing viable microbial

populations in aerosols and exhaust

gases released from the structure, and

document use of such features.

(f) Use systems for controlling

dissemination of the new

microorganism through other routes,

and document use of such features.

(g) Have in place emergency clean-up

procedures.

§ 725.424 Requirements for the Tier I

exemption.

(a) Conditions of exemption. The

manufacture or import of a new

microorganism for commercial purposes

is not subject to review under this part

if all of the following conditions are met

for all activities involving the new

microorganism:

(1) The recipient microorganism is

listed in and meets any requirements

specified in § 725.420.

(2) The introduced genetic material

meets the criteria under § 725.421.

(3) The physical containment and

control technologies of any facility in

which the microorganism will be

manufactured, processed, or used meet

the criteria under § 725.422.

(4) The manufacturer or importer

submits a certification described in

paragraph (b) of this section to EPA at

least 10 days before commencing initial

manufacture or import of a new

microorganism derived from a recipient

microorganism listed in § 725.420.

(5) The manufacturer or importer

complies with the recordkeeping

requirements of § 725.65 and maintains

records for the initial and subsequent

uses of the new microorganism that

verify compliance with the following:

(i) The certifications made in

paragraph (b) of this section.

(ii) All the eligibility criteria for the

Tier I exemption including the criteria

for the recipient microorganism, the

introduced genetic material, the

physical containment and control

technologies.

(b) Certification. To be eligible for the

Tier I exemption under this subpart, the

manufacturer or importer must submit

to EPA a document signed by a

responsible company official containing

the information listed in this paragraph.

(1) Name and address of manufacturer

or importer.

(2) Date when manufacture or import

is expected to begin.

(3) The identification (genus, species)

of the recipient microorganism listed in

§ 725.420 which is being used to create

the new microorganism which will be

used under the conditions of the Tier I

exemption.

(4) Certification of the following:

(i) Compliance with the introduced

genetic material criteria described in

§ 725.421.
17954 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

(ii) Compliance with the containment

requirements described in § 725.422,

including the provision in paragraph

(a)(3) of this section.

(5) The site of waste disposal and the

type of permits for disposal, the permit

numbers and the institutions issuing the

permits.

(6) The certification statement

required in § 725.25(b). Certification of

submission of test data is not required

for the Tier I exemption.

§ 725.426 Applicability of the Tier I

exemption.

The Tier I exemption under § 725.424

applies only to a manufacturer or

importer of a new microorganism that

certifies that the microorganism will be

used in all cases in compliance with

§§ 725.420, 725.421, and 725.422.

§ 725.428 Requirements for the Tier II

exemption.

The manufacturer or importer of a

new microorganism for commercial

purposes may submit to EPA a Tier II

exemption request in lieu of a MCAN

under subpart D of this part if all of the

following conditions are met:

(a) The recipient microorganism is

listed in and meets any requirements

specified in § 725.420.

(b) The introduced genetic material

meets the criteria under § 725.421.

(c) Adequate physical containment

and control technologies are used. The

criteria listed under § 725.422 for

physical containment and control

technologies of facilities should be used

as guidance to satisfy the Tier II

exemption request data requirements

listed at § 725.455(d). EPA will review

proposed process and containment

procedures as part of the submission for

a Tier II exemption under this section.

§ 725.450 Procedural requirements for the

Tier II exemption.

General requirements for all

submissions under this part are

contained in § 725.25. In addition, the

following requirements apply to

requests submitted under this subpart:

(a) Prenotice consultation. EPA

strongly suggests that for a Tier II

exemption, the submitter contact the

Agency for a prenotice consultation

regarding eligibility for the exemption.

(b) When to submit the Tier II

exemption request. Each person who is

eligible to submit a Tier II exemption

request under this subpart must submit

the request at least 45 calendar days

before the person intends to commence

manufacture or import.

(c) Contents of the Tier II exemption

request. Each person who submits a

request under this subpart must provide

the information described in §§ 725.428

and 725.455, as well as information

known to or reasonably ascertainable by

the person that would permit EPA to

determine that use of the

microorganism, under the conditions

specified in the request, will not present

an unreasonable risk of injury to health

or the environment.

(d) Recordkeeping. Each person who

submits a request under this subpart

must comply with the recordkeeping

requirements of § 725.65. In addition,

the submitter should maintain records

which contain information that verifies

compliance with the following:

(1) The certifications made in the

request.

(2) All the eligibility criteria for the

Tier II exemption request including the

criteria for the recipient microorganism,

the introduced genetic material, the

physical containment and control

technologies.

§ 725.455 Information to be included in the

Tier II exemption request.

The submitter must indicate clearly

that the submission is a Tier II

exemption request for a microorganism

instead of the MCAN under subpart D

of this part and must submit the

following information:

(a) Submitter identification. (1) The

name and headquarters address of the

submitter.

(2) The name, address, and office

telephone number (including area code)

of the principal technical contact

representing the submitter.

(b) Microorganism identity

information. (1) Identification (genus,

species, and strain) of the recipient

microorganism. Genus, species

designation should be substantiated by

a letter from a culture collection or a

brief summary of the results of tests

conducted for taxonomic identification.

(2) Type of genetic modification and

the function of the introduced genetic

material.

(3) Site of insertion.

(4) Certification of compliance with

the introduced genetic material criteria

described in § 725.421.

(c) Production volume. Production

volume, including total liters per year,

and the maximum cell concentration

achieved during the production process.

(d) Process and containment

information. (1) A description of the

process including the following:

(i) Identity and location of the

manufacturing site(s).

(ii) Process flow diagram illustrating

the production process, including

downstream separations, and indicating

the containment envelope around the

appropriate equipment.

(iii) Identities and quantities of

feedstocks.

(iv) Sources and quantities of

potential releases to both the workplace

and environment, and a description of

engineering controls, inactivation

procedures, and other measures which

will reduce worker exposure and

environmental releases.

(v) A description of procedures which

will be undertaken to prevent fugitive

emissions, i.e. leak detection and repair

program.

(vi) A description of procedures/

safeguards to prevent and mitigate

accidental releases to the workplace and

the environment.

(2) Certification of those elements of

the containment criteria described in

§ 725.422 with which the manufacturer

is in compliance, including stating by

number the elements with which the

manufacturer is in full compliance.

(e) The site of waste disposal and the

type of permits for disposal, the permit

numbers and the institutions issuing the

permits.

(f) The certification statement

required in § 725.25(b). Certification of

submission of test data is not required

for the Tier II exemption.

§ 725.470 EPA review of the Tier II

exemption request.

General procedures for review of all

submissions under this part are

contained in §§ 725.28 through 725.60.

In addition, the following procedures

apply to EPA review of Tier II

exemption requests submitted under

this subpart:

(a) Length of the review period. The

review period for the request will be 45

days from the date the Document

Control Officer for the Office of

Pollution Prevention and Toxics

receives a complete request, or the date

EPA determines the request is complete

under § 725.33, unless the Agency

extends the review period for good

cause under § 725.56.

(b) Criteria for review. EPA will

review the request to determine that the

new microorganism complies with

§ 725.428 and that its manufacture,

processing, use, and disposal as

described in the request will not present

an unreasonable risk of injury to health

or the environment.

(c) EPA decision regarding the Tier II

exemption request. A decision

concerning a request under this subpart

will be made by the Administrator, or a

designee.

(d) Determination that the

microorganism is ineligible for a Tier II

review. (1) EPA may determine that the

manufacturer or importer is not eligible

for Tier II review, because the

microorganism does not meet the

criteria under § 725.428 or the
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17955

Administrator, or a designee, decides

that there is insufficient information to

determine that the conditions of

manufacture, processing, use, or

disposal of the microorganism as

described in the request will not present

an unreasonable risk to health or the

environment.

(2) If the Agency makes this

determination, the Administrator, or a

designee will notify the manufacturer or

importer by telephone, followed by a

letter, that the request has been denied.

The letter will explain reasons for the

denial.

(3) If the request is denied, the

manufacturer or importer may submit

the information necessary to constitute

a MCAN under subpart D of this part.

(e) Approval or denial of the Tier II

exemption request. (1) No later than 45

days after EPA receives a request, the

Agency will either approve or deny the

request.

(2) In approving a request, EPA may

impose any restrictions necessary to

ensure that the microorganism will not

present an unreasonable risk of injury to

health and the environment as a result

of general commercial use.

(f) EPA may seek to enjoin the

manufacture or import of a

microorganism in violation of this

subpart, or act to seize any

microorganism manufactured or

imported in violation of this section or

take other actions under the authority of

sections 7 or 17 of the Act.

(g) A manufacturer or importer may

only proceed after receipt of EPA

approval.

Subparts H–K—[Reserved]

Subpart L—Additional Procedures for

Reporting on Significant New Uses of

Microorganisms

§ 725.900 Scope and purpose.

(a) This subpart describes additional

provisions governing submission of

MCANs for microorganisms subject to

significant new use rules identified in

subpart M of this part.

(b) Manufacturers, importers, and

processors described in § 725.105(c)

must submit a MCAN under subpart D

of this part for significant new uses of

microorganisms described in subpart M

of this part, unless they are excluded

under §§ 725.910 or 725.912.

(c) Section 725.920 discusses exports

and imports.

(d) Additional recordkeeping

requirements specific to significant new

uses of microorganisms are described in

§ 725.950.

(e) Section 725.975 describes how

EPA will approve alternative means of

complying with significant new use

requirements designated in subpart M of

this part.

(f) Expedited procedures for

promulgating significant new use

requirements under subpart M of this

part for microorganisms subject to

section 5(e) orders are discussed in

§§ 725.980 and 725.984.

(g) This subpart L contains provisions

governing submission and review of

notices for the microorganisms and

significant new uses identified in

subpart M of this part. The provisions

of this subpart L apply to the

microorganisms and significant new

uses identified in subpart M of this part,

except to the extent that they are

specifically modified or supplanted by

specific requirements in subpart M of

this part. In the event of a conflict

between the provisions of this subpart L

and the provisions of subpart M of this

part, the provisions of subpart M of this

part shall govern.

(h) The provisions of subparts A

through F of this part also apply to

subparts L and M of this part. For

purposes of subparts L and M of this

part, wherever the words

‘‘microorganism’’ or ‘‘new

microorganism’’ appear in subparts A

through F of this part, it shall mean the

microorganism subject to subparts L and

M of this part. In the event of a conflict

between the provisions of subparts A

through F and the provisions of subparts

L and M of this part, the provisions of

subparts L and M of this part shall

govern.

§ 725.910 Persons excluded from

reporting significant new uses.

(a) A person who intends to

manufacture, import, or process a

microorganism identified in subpart M

of this part and who intends to

distribute it in commerce is not required

to submit a MCAN under subpart D of

this part, if that person can document

one or more of the following as to each

recipient of the microorganism from that

person:

(1) That the person has notified the

recipient, in writing, of the specific

section in subpart M of this part which

identifies the microorganism and its

designated significant new uses, or

(2) That the recipient has knowledge

of the specific section in subpart M of

this part which identifies the

microorganism and its designated

significant new uses, or

(3) That the recipient cannot

undertake any significant new use

described in the specific section in

subpart M of this part.

(b) The manufacturer, importer, or

processor described in paragraph (a) of

this section must submit a MCAN under

subpart D of this part, if such person has

knowledge at the time of commercial

distribution of the microorganism

identified in the specific section in

subpart M of this part that a recipient

intends to engage in a designated

significant new use of that

microorganism without submitting a

MCAN under this part.

(c) A person who processes a

microorganism identified in a specific

section in subpart M of this part for a

significant new use of that

microorganism is not required to submit

a MCAN if that person can document

each of the following:

(1) That the person does not know the

specific microorganism identity of the

microorganism being processed, and

(2) That the person is processing the

microorganism without knowledge that

the microorganism is identified in

subpart M of this part.

(d)(1) If at any time after commencing

distribution in commerce of a

microorganism identified in a specific

section in subpart M of this part, a

person who manufactures, imports, or

processes a microorganism described in

subpart M of this part and distributes it

in commerce has knowledge that a

recipient of the microorganism is

engaging in a significant new use of that

microorganism designated in that

section without submitting a MCAN

under this part, the person is required

to cease supplying the microorganism to

that recipient and to submit a MCAN for

that microorganism and significant new

use, unless the person is able to

document each of the following:

(i) That the person has notified the

recipient and EPA enforcement

authorities (at the address in paragraph

(d)(1)(iii) of this section), in writing

within 15 working days of the time the

person develops knowledge that the

recipient is engaging in a significant

new use, that the recipient is engaging

in a significant new use without

submitting a MCAN.

(ii) That, within 15 working days of

notifying the recipient as described in

paragraph (d)(1)(i) of this section, the

person received from the recipient, in

writing, a statement of assurance that

the recipient is aware of the terms of the

applicable section in subpart M of this

part and will not engage in the

significant new use.

(iii) That the person has promptly

provided EPA enforcement authorities

with a copy of the recipient’s statement

of assurance described in paragraph

(d)(1)(ii) of this section. The copy must

be sent to the Director, Office of

Compliance (2221A), Environmental

Protection Agency, 401 M St., SW.,

Washington, DC 20460.
17956 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

(2) If EPA notifies the manufacturer,

importer, or processor that the recipient

is engaging in a significant new use after

providing the statement of assurance

described in paragraph (d)(1)(ii) of this

section and without submitting a MCAN

under this part, the manufacturer,

importer, or processor shall

immediately cease distribution to that

recipient until the manufacturer,

importer, or processor or the recipient

has submitted a MCAN under this part

and the MCAN review period has

ended.

(3) If, after receiving a statement of

assurance from a recipient under

paragraph (d)(1)(ii) of this section, a

manufacturer, importer, or processor

has knowledge that the recipient is

engaging in a significant new use

without submitting a MCAN under this

part, the manufacturer, importer, or

processor must immediately cease

distributing the microorganism to that

recipient and notify EPA enforcement

authorities at the address identified in

paragraph (d)(1)(iii) of this section. The

manufacturer, importer, or processor

may not resume distribution to that

recipient until any one of the following

has occurred:

(i) The manufacturer, importer, or

processor has submitted a MCAN under

this part and the MCAN review period

has ended.

(ii) The recipient has submitted a

MCAN under this part and the MCAN

review period has ended.

(iii) The manufacturer, importer, or

processor has received notice from EPA

enforcement authorities that it may

resume distribution to that recipient.

§ 725.912 Exemptions.

Persons identified in § 725.105(c) are

not required to submit a MCAN under

subpart D of this part for a

microorganism identified in subpart M

of this part, unless otherwise specified

in a specific section in subpart M, if:

(a) The person submits a MCAN for

the microorganism prior to the

promulgation date of the section in

subpart M of this part which identifies

the microorganism, and the person

receives written notification of

compliance from EPA prior to the

effective date of such section. The

MCAN submitter must comply with any

applicable requirement of section 5(b) of

the Act. The MCAN must include the

information and test data specified in

section 5(d)(1) of the Act. For purposes

of this exemption, the specific section in

subpart M of this part which identifies

the microorganism and §§ 725.3, 725.15,

725.65, 725.70, 725.75, 725.100, and

725.900 apply; after the effective date of

the section in subpart M of this part

which identifies the microorganism,

§§ 725.105 and 725.910 apply and

§ 725.920 continues to apply. EPA will

provide the MCAN submitter with

written notification of compliance only

if one of the following occurs:

(1) EPA is unable to make the finding

that the activities described in the

MCAN will or may present an

unreasonable risk of injury to health or

the environment under reasonably

foreseeable circumstances, or

(2) EPA and the person negotiate a

consent order under section 5(e) of the

Act, such order to take effect on the

effective date of the section in subpart

M of this part which identifies the

microorganism.

(b) The person is operating under the

terms of a consent order issued under

section 5(e) of the Act applicable to that

person. If a provision of such section

5(e) order is inconsistent with a specific

significant new use identified in subpart

M of this part, abiding by the provision

of the section 5(e) order exempts the

person from submitting a MCAN for that

specific significant new use.

§ 725.920 Exports and imports.

(a) Exports. Persons who intend to

export a microorganism identified in

subpart M of this part, or in any

proposed rule which would amend

subpart M of this part, are subject to the

export notification provisions of section

12(b) of the Act. The regulations that

interpret section 12(b) appear at part

707 of this chapter.

(b) Imports. Persons who import a

substance identified in a specific section

in subpart M of this part are subject to

the import certification requirements

under section 13 of the Act, which are

codified at 19 CFR §§ 12.118 through

12.127 and 127.28(i). The EPA policy in

support of the import certification

requirements appears at part 707 of this

chapter.

§ 725.950 Additional recordkeeping

requirements.

Persons submitting a MCAN for a

significant new use of a microorganism

must comply with the recordkeeping

requirements of § 725.65. In addition,

the following requirements apply:

(a) At the time EPA adds a

microorganism to subpart M of this part,

EPA may specify appropriate

recordkeeping requirements. Each

manufacturer, importer, and processor

of the microorganism shall maintain the

records for 3 years from the date of their

creation.

(b) The records required to be

maintained under this section may

include the following:

(1) Records documenting the

information contained in the MCAN

submitted to EPA.

(2) Records documenting the

manufacture and importation volume of

the microorganism and the

corresponding dates of manufacture and

import.

(3) Records documenting volumes of

the microorganism purchased

domestically by processors of the

microorganism, names and addresses of

suppliers and corresponding dates of

purchase.

(4) Records documenting the names

and addresses (including shipment

destination address, if different) of all

persons outside the site of manufacture

or import to whom the manufacturer,

importer, or processor directly sells or

transfers the microorganism, the date of

each sale or transfer, and the quantity of

the microorganism sold or transferred

on such date.

§ 725.975 EPA approval of alternative

control measures.

(a) In certain sections of subpart M of

this part, significant new uses for the

identified microorganisms are described

as the failure to establish and

implement programs providing for the

use of either: specific measures to

control worker exposure to or release of

microorganisms which are identified in

such sections, or alternative measures to

control worker exposure or

environmental release which EPA has

determined provide substantially the

same degree of protection as the

specified control measures. Persons who

manufacture, import, or process a

microorganism identified in such

sections and who intend to employ

alternative measures to control worker

exposure or environmental release must

submit a request to EPA for a

determination of equivalency before

commencing manufacture, import, or

processing involving the alternative

control measures.

(b) A request for a determination of

equivalency must be submitted in

writing to the Office of Pollution

Prevention and Toxics, Document

Control Officer, 7407, 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.
Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations 17957

(5) The specifications of the

alternative worker exposure control

measures or environmental release

control measures.

(6) A detailed analysis explaining

why such alternative control measures

provide substantially the same degree of

protection as the specific control

measures identified in the specific

section in subpart M of this part which

pertains to the microorganism for which

the request is being submitted.

(7) The data and information

described in §§ 725.155 and 725.160. If

such data and information have already

been submitted to EPA’s Office of

Pollution Prevention and Toxics, the

submitter need only document that it

was previously submitted, to whom,

and the date it was submitted.

(c) Requests for determinations of

equivalency will be reviewed by EPA

within 45 days. Determinations under

this paragraph will be made by the

Director, or a designee. Notice of the

results of such determinations will be

mailed to the submitter.

(d) If EPA notifies the submitter under

paragraph (c) of this section that EPA

has determined that the alternative

control measures provide substantially

the same degree of protection as the

specified control measures identified in

the specific section of subpart M of this

part which pertains to the

microorganism for which the request is

being submitted, the submitter may

commence manufacture, import, or

processing in accordance with the

specifications for alternative worker

exposure control measures or

environmental release control measures

identified in the submitter’s request,

and may alter any corresponding

notification to workers to reflect such

alternative controls. Deviations from the

activities described in the EPA

notification constitute a significant new

use and are subject to the requirements

of this part.

§ 725.980 Expedited procedures for

issuing significant new use rules for

microorganisms subject to section 5(e)

orders.

(a) Selection of microorganisms. (1) In

accordance with the expedited process

specified in this section, EPA will issue

significant new use notification

requirements for each new

microorganism that, after MCAN review

under subpart D of this part, becomes

subject to a final order issued under

section 5(e) of the Act, except for an

order that prohibits manufacture and

import of the microorganism, unless

EPA determines that significant new use

notification requirements are not

needed for the microorganism.

(2) If EPA determines that significant

new use notifications requirements are

not needed for a microorganism that is

subject to a final order issued under

section 5(e) of the Act, EPA will issue

a notice in the Federal Register

explaining why the significant new use

requirements are not needed.

(b) Designation of requirements. (1)

The significant new use notification and

other specific requirements will be

based on and be consistent with the

provisions included in the final order

issued for the microorganism under

section 5(e) of the Act. EPA may also

designate additional activities as

significant new uses which will be

subject to notification.

(2) Significant new use requirements

and other specific requirements

designated under this section will be

listed in subpart M of this part. For each

microorganism, subpart M of this part

will identify:

(i) The microorganism name.

(ii) The activities designated as

significant new uses.

(iii) Other specific requirements

applicable to the microorganism,

including recordkeeping requirements

or any other requirements included in

the final section 5(e) order.

(c) Procedures for issuing significant

new use rules. (1) Possible processes.

EPA will issue significant new use rules

(SNURs) under this section by one of

the following three processes: direct

final rulemaking, interim final

rulemaking, or notice and comment

rulemaking. EPA will use the direct

final rulemaking process to issue

significant new use rules unless it

determines that, in a particular case, one

of the other processes is more

appropriate.

(2) Notice in the Federal Register.

Federal Register documents issued to

propose or establish significant new

uses under this section will contain the

following:

(i) The microorganism identity or, if

its specific identity is claimed

confidential, an appropriate generic

microorganism name and an accession

number assigned by EPA.

(ii) The MCAN number.

(iii) A summary of EPA’s findings

under section 5(e)(1)(A) of the Act for

the final order issued under section 5(e).

(iv) Designation of the significant new

uses subject to, or proposed to be

subject to, notification and any other

applicable requirements.

(v) Any modification of subpart L of

this part applicable to the specific

microorganism and significant new

uses.

(vi) If the Federal Register document

establishes a final rule, or notifies the

public that a final rule will not be

issued after public comment has been

received, the document will describe

comments received and EPA’s response.

(3) Direct final rulemaking. (i) EPA

will use direct final rulemaking to issue

a significant new use rule, when

specific requirements will be based on

and be consistent with the provisions

included in the final order issued for the

microorganism under section 5(e) of the

Act. EPA will issue a final rule in the

Federal Register following its decision

to develop a significant new use rule

under this section for a specific new

microorganism.

(ii) The Federal Register document

will state that, unless written notice is

received by EPA within 30 days of

publication that someone wishes to

submit adverse or critical comments, the

rule will be effective 60 days from the

date of publication. The written notice

of intent to submit adverse or critical

comments should state which SNUR(s)

will be the subject of the adverse or

critical comments, if several SNURs are

established through the direct final rule.

If notice is received within 30 days that

someone wishes to submit adverse or

critical comments, the section(s) of the

direct final rule containing the SNUR(s)

for which a notice of intent to comment

was received will be withdrawn by EPA

issuing a document in the final rule

section of the Federal Register, and a

proposal will be published in the

proposed rule section of the Federal

Register. The proposal will establish a

30–day comment period.

(iii) If EPA, having considered any

timely comments submitted in response

to the proposal, decides to establish

notification requirements under this

section, EPA will issue a final rule

adding the microorganism to subpart M

of this part and designating the

significant new uses subject to

notification.

(4) Interim final rulemaking. (i) EPA

will use the interim final rulemaking

procedure to issue a significant new use

rule, when specific requirements will be

based on and be consistent with the

provisions included in the final order

issued for the microorganism under

section 5(e) of the Act. The Agency will

issue an interim final rule in the Federal

Register following its decision to

develop a significant new use rule for a

specific new microorganism. The

document will state EPA’s reasons for

using the interim final rulemaking

procedure.

(A) The significant new use rule will

take effect on the date of publication.

(B) Persons will be given 30 days from

the date of publication to submit

comments.
17958 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

(ii) Interim final rules issued under

this section shall cease to be in effect

180 days after publication unless,

within the 180–day period, EPA issues

a final rule in the Federal Register

responding to any written comments

received during the 30–day comment

period specified in paragraph (c)(4)(i)(B)

of this section and promulgating final

significant new use notification

requirements and other requirements for

the microorganism.

(5) Notice and comment rulemaking.

(i) EPA will use a notice and comment

procedure to issue a significant new use

rule, when EPA is designating

additional activities which are not

provisions included in the final order

issued for the microorganism under

section 5(e) of the Act as significant new

uses which will be subject to

notification. EPA will issue a proposal

in the Federal Register following its

decision to develop a significant new

use rule under this section for a specific

new microorganism. Persons will be

given 30 days to comment on whether

EPA should establish notification

requirements for the microorganism

under this part.

(ii) If EPA, having considered any

timely comments, decides to establish

notification requirements under this

section, EPA will issue a final rule

adding the microorganism to subpart M

of this part and designating the

significant new uses subject to

notification.

(d) Schedule for issuing significant

new use rules. (1) Unless EPA

determines that a significant new use

rule should not be issued under this

section, EPA will issue a proposed rule,

a direct final rule, or an interim final

rule within 180 days of receipt of a valid

notice of commencement under

§ 725.190.

(2) If EPA receives adverse or critical

significant comments following

publication of a proposed or interim

final rule, EPA will either withdraw the

rule or issue a final rule addressing the

comments received.

§ 725.984 Modification or revocation of

certain notification requirements.

(a) Criteria for modification or

revocation. EPA may at any time modify

or revoke significant new use

notification requirements for a

microorganism which has been added to

subpart M of this part using the

procedures of § 725.980. Such action

may be taken under this section if EPA

makes one of the following

determinations, unless other

information shows that the

requirements should be retained:

(1) Test data or other information

obtained by EPA provide a reasonable

basis for concluding that activities

designated as significant new uses of the

microorganism will not present an

unreasonable risk of injury to health or

the environment.

(2) EPA has promulgated a rule under

section 4 or 6 of the Act, or EPA or

another agency has taken action under

another law, for the microorganism that

eliminates the need for significant new

use notification under section 5(a)(2) of

the Act.

(3) EPA has received MCANs for some

or all of the activities designated as

significant new uses of the

microorganism and, after reviewing

such MCANs, concluded that there is no

need to require additional notice from

persons who propose to engage in

identical or similar activities.

(4) EPA has examined new

information, or has reexamined the test

data or other information supporting its

finding under section 5(e)(1)(A)(ii)(I) of

the Act and has concluded that a

rational basis no longer exists for the

findings that activities involving the

microorganism may present an

unreasonable risk of injury to health or

the environment required under section

5(e)(1)(A) of the Act.

(5) Certain activities involving the

microorganism have been designated as

significant new uses pending the

completion of testing, and adequate test

data developed in accordance with

applicable procedures and criteria have

been submitted to EPA.

(b) Procedures for limitation or

revocation. Modification or revocation

of significant new use notification

requirements for a microorganism that

has been added to subpart M of this part

using the procedures described in

§ 725.980 may occur either at EPA’s

initiative or in response to a written

request.

(1) Any affected person may request

modification or revocation of significant

new use notification requirements for a

microorganism that has been added to

subpart M of this part using the

procedures described in § 725.980 by

writing to the Director, or a designee,

and stating the basis for such request.

The request must be accompanied by

information sufficient to support the

request. All requests should be sent to

the TSCA Document Processing Center

(7407), Room L–100, U.S.

Environmental Protection Agency, 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

§ 725.1000 Scope.

This subpart identifies uses of

microorganisms which EPA has

determined to be significant new uses

under the authority of section 5(a)(2) of

the Toxic Substances Control Act.

[FR Doc. 97–8669 Filed 4–10–97; 8:45 am]

BILLING CODE 6560–50–F