USDA-APHIS Biotechnology Regulatory Services

Request to Extend Nonregulated Status

from a Previous Determination:

Extension Guidance for Developers

v. 02/22/2016

Biotechnology Regulatory Services

Animal and Plant Health Inspection Service

United States Department of Agriculture

4700 River Road

Riverdale, MD 20737
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Table of Contents

Introduction to the Extension Process...........................................................................................................3

Extension Eligibility Considerations ..............................................................................................................3

Functional Equivalency Considerations......................................................................................................4

Crop Considerations.......................................................................................................................................... 4

Request for Extension of a Previous Determination of Nonregulated Status..................................5
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Introduction to the Extension Process

The Animal and Plant Health Inspection Service (APHIS) of the U.S. Department of Agriculture 

(USDA) has the responsibility, under the Plant Protection Act of 2000, to prevent the 

introduction and dissemination into the United States or interstate of plant pests. Under this 

authority, APHIS has published regulations found at 7 CFR part 340 pertaining to the 

introduction (importation, interstate movement, and release into the environment) of genetically 

engineered (GE) organisms and products derived from known plant pests (regulated articles). 

Before introducing a regulated article, a person is required under §340.0 of the regulations to 

either: (1) notify APHIS and receive an acknowledgement in accordance with §340.3 or (2) 

obtain a permit in accordance with §340.4. An organism is not subject to the regulations if it is 

determined that it is not a plant pest or after a thorough evaluation, the agency determines that it 

does not present a plant pest risk. The regulations at §340.6 entitled “Petition for determination 

of nonregulated status,” provide that a person may petition APHIS to evaluate submitted data 

requesting that APHIS determine that a regulated article is unlikely to pose a plant pest risk and 

will no longer be regulated. If APHIS determines that the regulated article does not present a risk 

of introduction or dissemination of a plant pest, the petition will be granted, thereby allowing 

unrestricted introduction of the article.

In addition, §340.6(e) of the regulations provides that APHIS may extend a determination of 

nonregulated status to other regulated articles upon finding that these regulated articles are 

sufficiently similar to one or more articles that have been granted nonregulated status because 

they do not present a risk of introduction or dissemination of a plant pest . Such a finding would 

be made based on an evaluation of the similarity of the regulated articles to antecedent 

organism(s), i.e., an organism(s) that has already been the subject of a determination of 

nonregulated status by APHIS under §340.6, and that is used as a reference for comparison to the 

regulated article(s) under consideration. 

For actions such as determinations of nonregulated status and extensions of nonregulated status, 

APHIS prepares environmental documentation as part of its obligations under the National 

Environmental Policy Act (NEPA) of 1969 and the APHIS NEPA implementing regulations at 7 

CFR part 372. Whenever possible, APHIS will use existing Environmental Assessments (EAs) 

or Environmental Impact Statements (EISs) for the antecedent organism(s). In some cases, only 

new Findings of No Significant Impact (FONSIs) will be required. In other cases, new EAs will 

be written to update relevant information from previous environmental documents and/or to 

combine the analysis from multiple environmental documents when there are multiple 

antecedents.

APHIS is providing the following guidance to help a person determine whether and how to 

prepare a request for an extension of a determination of nonregulated status. We recommend 

discussing your request for extension of nonregulated status with APHIS prior to submission. 

Extension Eligibility Considerations

The aim of making comparisons between regulated articles for which a person is seeking an 

extension of a determination of nonregulated status and antecedent organisms is to ensure that 
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the regulated articles under consideration are unlikely to pose plant pest risks beyond those 

considered in the initial determination of nonregulated status.

Functional Equivalency Considerations

In evaluating the similarity between two GE plants, APHIS considers whether the mechanismsof-action of the introduced traits are functionally equivalent. For example, one mechanism-ofaction for resistance in plants to the herbicide glyphosate relies on an inability of glyphosate 

molecules to bind and inactivate an enzyme called EPSPS, which is responsible for an essential 

step in a biochemical pathway for the synthesis of certain amino acids. If glyphosate cannot 

bind to the EPSPS enzyme, the plant is resistant to the herbicide. APHIS has granted 

nonregulated status to two very similar types of GE plants which differed in the donor organism 

for the epsps genes: one version of the gene was derived from corn (mepsps) and the other from a

strain of Agrobacterium (CP4 epsps). In both cases the added gene encodes an EPSPS protein 

which does not bind to glyphosate. These two glyphosate resistance traits have mechanisms-ofaction which are functionally equivalent, so either should be a suitable antecedent for the other. 

Glyphosate resistance can also be accomplished by other mechanisms-of-action. For example,

the protein glyphosate acetyl transferase (GAT) gives resistance by metabolizing glyphosate to 

an inactive form. Therefore, glyphosate resistance accomplished through GAT is not functionally 

equivalent to glyphosate resistance achieved by an added epsps gene. Therefore, a glyphosateresistant corn that uses a gat gene to achieve glyphosate resistance is not similar enough to be 

used as an antecedent for a glyphosate-resistant corn developed by adding an epsps gene. 

Crop Considerations

In addition to considering the mechanism-of-action of a particular trait, APHIS also considers the 

crop in which the trait is expressed. For instance, if APHIS had never reviewed an herbicideresistant soybean before, soybean transformed with an epsps gene (mepsps or cp4) would not be 

eligible for an extension based on an antecedent corn variety transformed with an epsps gene 

(i.e., the previously reviewed crop). However, if another herbicide-resistant soybean had been 

previously reviewed with a different herbicide resistance, such as a glufosinate-resistant soybean, 

APHIS would evaluate whether the extension process was appropriate for an EPSPS soybean 

based on two antecedents, the glufosinate-resistant soybean which has the same phenotype 

category (herbicide-resistance) and the EPSPS corn which has a functionally equivalent 

mechanism-of-action. Whether the extension process would be used would depend on the extent 

to which the agency identifies additional issues not previously addressed in the two prior 

reviews.

Thus, to be considered for the extension process, 1) APHIS must have made a prior 

determination of nonregulated status of the mechanism-of-action for the trait of interest in any 

crop, and 2) APHIS must have made a determination of nonregulated status for the phenotype 

category (e.g. herbicide resistance, insect resistance) in the subject crop. 

APHIS anticipates the extension process being applicable in the following cases:
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1) Where a previously reviewed trait is introduced into different varieties of the same 

crop. For example, various apple varieties genetically engineered with the same nonbrowning trait as in one of the antecedent Arctic® apple events in ‘Golden Delicious’ and 

‘Granny Smith’ varieties (10-161-01p).

2) Where traits previously reviewed separately in a particular crop are stacked into the 

same crop by introducing them together through genetic engineering. For example, a

stacked corn line is created by introducing both a mepsps gene (previously reviewed in 

corn) and a cry gene from Bacillus thuringiensis (previously reviewed in corn). In this 

case there will be two or more antecedents.

3) Where phenotype categories have been reviewed previously in the crop but a 

mechanism-of-action new to the crop has been reviewed in another crop. For example, if 

the hppd gene, which confers resistance to mesotrione herbicide, is introduced in corn 

(hppd was previously reviewed in soybean and many herbicide-resistant corn lines have 

been reviewed). In this case there will be two or more antecedents.

While the three cases are eligible for the extension process, the similarity of the product being 

considered for an extension (potential extension) to the antecedents decreases from case 1 to case 

3. Consequently the timelines for review may become longer as the degree of similarity 

decreases. There may be instances in case 3 where issues are different enough between the 

potential extension and the antecedent organism(s) that APHIS determines that the extension 

process is not appropriate and the petition process should be used. Also, because the potential 

extension is somewhat different, previous NEPA analyses may not be sufficient and additional

analyses may be required. Nevertheless, APHIS believes that most products that meet one of the 

three criteria are likely to qualify for the extension process, and that the review will be completed 

within eight months after receiving a complete dossier. 

Request for Extension of a Previous Determination of Nonregulated Status

For APHIS to grant an extension of a determination of nonregulated status to other regulated 

articles, the agency must determine that the new regulated articles in question raise no new issues 

meriting separate review under the petition process. Including the following information in the 

submitter’s dossier will facilitate APHIS’ review of extension request:

• A complete description of the genotype and phenotype of the regulated article(s). This 

includes a description of the following:

o Genetic modifications in the regulated article(s) under consideration.

o Function and donor organisms for any inserted genetic material.

o Transformation vector.

o Mechanism-of-action of the genetic modification.
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o Compositional analysis (not typically required but may be requested) when the trait may 

be expected to cause changes to metabolites or compounds which could affect the plant 

pest risk.

• A molecular characterization of the regulated article.

• A complete, concise, written narrative comparison and summary table of the antecedent

organism(s) and the regulated article. This characterization may demonstrate that the 

modifications in the regulated articles are of one or more of the types illustrated in the

eligibility considerations discussed above.

• Information on the phenotypic expression of the genetic modifications in the regulated 

article(s) and any known differences in phenotype between the regulated article(s) and their 

antecedent organism(s). These known differences should be further categorized as to whether 

they are expected based on the intended effect of the new modifications.

• The petition number(s) of the determinations from which this extension is requested.