1

GUIDE FOR SUBMITTING PERMIT APPLICATIONS FOR MICROORGANISMS 

DEVELOPED USING GENETIC ENGINEERING UNDER 7 CFR PART 340

RESPONSE TO COMMENTS

On March 23, 2023, APHIS BRS released a dra� guide for submi�ng permit applica�ons under 7 CFR part 

340 for microorganisms that have been developed using gene�c engineering. BRS invited the public to 

review and comment on the dra�, resul�ng in feedback from 24 individuals and organiza�ons (one 

organiza�on’s leter contained 2,149 undersigned names). This document summarizes and addresses the 

comments BRS received on the dra� guide and clarifies whether any changes were made based on the 

feedback received.

We received comments on a range of different issues and grouped the comments into the following 

categories:

• Permit applica�on data requirements

• Principle risk propor�onality when determining data requirements

• Permit requirements when conduc�ng research in a contained facility

• Coordina�on among regulatory agencies

• Clarifica�on on modified microbes that are excluded or exempted from 7 CFR part 340

Beyond these categories, we also received comments related to how BRS verifies the informa�on in 

permit applica�ons, enhancing the Standard Opera�ng Procedures (SOPs) that accompany permit

applica�ons, and requests for establishing a Regulatory Status Review (RSR) along with regulatory 

exemp�ons for modified microbes to support their commercializa�on.

Comments about labelling and general comments about ecosystem service provided by microbes are out 

of scope for the guide, and BRS will not address them here.

Comments about permit applica�on data requirements 

1. Commenters asked BRS to clarify the data requirements for obtaining a permit for field trials; others

said BRS should require more data and conduct a thorough environmental analysis before issuing a 

permit.

2. Commenters expressed the concern that BRS requires too much data and informa�on in permit 

applica�ons.

3. Some commenters believed the processing �me for permits was too long, including delays 

associated with incomplete submissions. Conversely, one ques�oned whether a 45 day-�me frame is 

adequate to review an import and/or interstate movement permit. 

Response:

The USDA established biotechnology regula�ons in 1987 and has made seven amendments since then. 

The regula�ons require similar informa�on for both plant and non-plant organisms, including microbes, 

for both shipments and environmental releases to assure their containment or confinement. For 

example, all applica�ons to move a modified organism must include informa�on on the molecular 

change, trait, and the method of shipment to ensure the organism is securely contained. Likewise, 

applica�ons for permits involving environmental releases must include informa�on on the molecular 

change, traits, and the procedures the developer will use to ensure confinement to prevent the escape, 

spread, and persistence in authorized loca�ons. The data requirements for permits are tailored to 

support the Plant Protec�on Act’s protec�on goal of preven�ng the unauthorized release of regulated 

materials into the environment.
2

Our experience with both plant and non-plant organism permits indicates that early consulta�ons with 

BRS about planned research and permit requirements, along with �mely submission of the necessary 

informa�on, are crucial to achieve �mely permit issuance. During consulta�ons involving modified 

microbes, BRS and developers review a summary of the informa�on requirements for the permit 

applica�on. Developers have reported that these consulta�ons make it easier for them to meet the 

permit applica�on requirements. We have incorporated this informa�on into the guide because of its 

u�lity to developers and interested par�es. These consulta�ons, together with guides and other 

informa�on available on our website, are intended to help first-�me and returning permit applicants 

navigate the permi�ng process and improve the efficiency of the permi�ng process. Finally, BRS has

reorganized the guide to highlight required informa�on in the main body of the document and placed 

the probing ques�ons developers should think about when developing SOPs (“considera�ons”) in the 

Appendix to make clear that answers to these ques�ons are not part of the permit applica�on. In terms 

of commenters who believed we should require more informa�on on permit applica�ons, based on our 

experience, we believe the permit applica�on and accompanying SOPs provide adequate informa�on for 

BRS to establish any necessary supplemental permit condi�ons to ensure the containment or 

confinement of modified microbes. 

4. Some commenters noted that revisions to regula�ons and guidelines for organisms developed using 

gene�c engineering can be unexpected for applicants who are familiar with legacy regula�ons and

previous guidelines. Other commenters noted that the approval process for permit applica�ons can 

take several months or even years, depending on the complexity of the applica�on and may require

further informa�on, which may surprise applicants who are expec�ng a faster approval.

Response: 

As noted above, BRS established biotechnology regula�ons in 1987 and has revised the regula�ons 

seven �mes since then. When undertaking a revision, BRS uses no�ce-and-comment rulemaking to 

ensure the public has an opportunity to review and provide feedback on a proposed rule before USDA 

issues and implements a final rule. With the most recent regulatory revisions (the most significant 

update since 1987), BRS used a phased approach to implemen�ng the revised regula�ons to allow 

developers �me to update and align business processes with the revised regula�ons. BRS also maintains 

a stakeholder registry and uses this tool to share regulatory and process updates to avoid surprise and 

ensure stakeholders have an opportunity to visit with BRS and ask ques�ons related to the revised 

regula�ons. 

Regarding permit �melines, the regula�ons specify that a permit applica�on for shipment will be 

approved within 45 days, while field release applica�ons may take up to 120 days. Delays can occur if a

permit applica�on does not contain the necessary informa�on, which can prolong the review and 

issuance process. The purpose of the guide is to support developers in providing complete permit 

applica�ons when they first submit them to enable efficient and �mely review.

5. Some commenters suggested that BRS consider the poten�al for horizontal gene transfer (HGT) 

between microbes when evalua�ng the environmental risk and worry the permit guide may not 

adequately address the long-term impact of microorganisms on the environment or the risk of HGT 

to other organisms. 

Response:

BRS considers the poten�al for horizontal gene transfer (HGT) when evalua�ng microbe permit 

applica�ons. For example, BRS considers whether the modifica�on to the microbe is associated with 
3

fitness-enhancing traits. In this context, BRS considers the circumstances that may present a poten�al 

plant pest risk and tailors the permit condi�ons to prevent such risks. Permit condi�ons require that all 

modified microbes in confined field trials, including those that received modified traits through HGT, 

should not persist or spread from the regulated field trial at its conclusion. If spraying modified microbes 

onto plant parts poses a poten�al risk of insect vectors transmi�ng the modified microbe to 

nonregulated plants and facilita�ng HGT between modified and wild-type microbes, the permit 

condi�ons will include measures to prevent vector transmission.

Comments about the Principle of Risk propor�onality when determining data requirements

1. We received a comment that BRS’ approach to regula�ng microbes under 7 CFR part 340, is overly 

cau�ous, leading to duplica�on and inconsistency with other agencies such as such as Plant 

Protec�on and Quaran�ne (PPQ) and the U.S. Environmental Protec�on Agency (EPA). 

2. Another commenter asked BRS to find ways to acknowledge these sister agencies' evalua�ons to 

reduce duplica�on and ensure that permit condi�ons are based on clear risk evalua�ons. The 

organiza�on asked BRS to define the data and informa�on required for field release permits to focus 

on actual (rather than hypothe�cal) risks and encouraged BRS to allocate sufficient resources to 

develop a process based on objec�ve scien�fic criteria that provides a regulatory offramp for

microbial products, if warranted.

Response:

BRS and EPA have separate regula�ons for modified microbes. BRS focuses on assessing whether the 

modified microbes pose an increased plant pest risk compared to their original form, while EPA regulates

modified organisms intended for pes�cidal purposes under the Federal Insec�cide Fungicide and 

Roden�cide Act (FIFRA) and the Federal Food Drug and Cosme�c Act (FFDCA), or if used as biofer�lizers, 

bioremedia�on agents, and for the produc�on of various industrial compounds, including biofuels under 

the Toxic Substances Control Act (TSCA). Although some data requirements may vary based on agency 

specific regula�ons, we agree there is an opportunity for greater alignment. In addi�on to con�nuing to 

hold regular mee�ngs to share informa�on about modified microbes under each agencies’ review, BRS 

will work with EPA to streamline and align its data requirements where possible. To allow this work to 

proceed, BRS is pos�ng this guide as a second dra� and in the future will refine, as possible, informa�on

requirements for permit applica�ons.

3. A commenter stated that BRS’ current regula�on of modified microbes captures products outside 

the scope of the agency’s authority under the Plant Protec�on Act, imposes burdensome and 

inflexible field trial condi�ons and requirements that increase research and development costs, and 

provides no regulatory off ramp for oversight under 7 CFR part 340. Other comments shared the 

concern that BRS’ revised regula�on do not provide a comparable pathway for the 

commercializa�on of modified microbes like Regulatory Status Review or (RSR) or Confirma�on of 

Exemp�on Request (CR) does for modified plants.

Response:

BRS’ regula�on of modified microbes is based on the Plant Protec�on Act’s authority to regulate plant 

pests and biological control organisms intended to control plant pests. This includes gene�cally modified 

biological control organisms that could harm non-target beneficial organisms such as invertebrate 

predators, pollinators, or microbes that promote plant health. As these organisms are introduced into 

the environment, we must consider both their direct and indirect effects on non-target organisms that 

are beneficial to agriculture. If a modified organism is known to have harmful impacts on beneficial nontarget organisms, it is within APHIS' authority under the PPA to restrict its release. If there is uncertainty 
4 

regarding the organism's impact on beneficial non-target organisms, BRS may regulate its movement and 

release un�l there is a beter understanding of its effects.

With that said, to further address the concerns, BRS will explore poten�al regulatory changes that would 

exempt from 7 CFR part 340, in whole or in part, modified biological control organisms that are not 

plants pests and are registered with EPA as microbial pes�cides or are not EPA registered pes�cides but 

are being transferred, sold, or distributed in accordance with EPA’s regula�ons at 40 CFR 152.30. BRS will

also explore poten�al mechanisms for risk-based de-regula�on of non-plant organisms that could be 

proposed in future rulemaking, including by considering comments from stakeholders on the dra� guide, 

the Request for Informa�on associated with Execu�ve Order 14081, and further engaging developers 

and other stakeholders. 

4. A commenter raised concerns about BRS’ interpreta�on of its authority under the Plant Protec�on 

Act regarding microbes no�ng that, in the past, the regula�ons listed the organisms that were 

considered "plant pests." The commenter noted that the current 7 CFR part 340 lacks clear 

guidelines and instead relies on undefined criteria, leading to a more precau�onary approach rather 

than a risk-based one. The commenter asked that BRS use more concrete sources of guidance, such 

as the criteria used by PPQ, to improve transparency and clarity. 

Response: 

In the legacy biotechnology regula�ons, BRS maintained a regulatory lis�ng of taxa to describe 

“organisms that are or contain plant pests” to aid developers in determining whether a modified 

organism required a USDA permit. When BRS updated its regula�ons in 2020, it removed this lis�ng from 

the regula�ons because it had become out-of-date. BRS recognized that taxonomic designa�ons 

some�mes change, and new plant pests are con�nually discovered. As such, rather than maintaining a 

sta�c list of taxa in the regula�ons, BRS agreed to post a list of taxa on its website that could be regularly 

reviewed and updated. We agree that the availability of this plant pest taxa list plays an important role in 

providing clarity on BRS regulatory scope and permi�ng requirements. BRS will partner with subject 

mater experts to develop, maintain, and update a plant pest list. BRS plans to implement its partnership 

and begin development of the plant pest list in fiscal year 2024. 

Addi�onally, BRS collaborates with PPQ to determine the plant pest status of wild-type microbes before 

deciding the plant pest status of their modified versions. PPQ and BRS have established a working group 

to address areas of ambiguity related to a microbe’s regulatory status, with a goal of harmonizing, as 

possible, informa�on and data requirements for modified and non-modified microbes regulated under 

the Plant Protec�on Act. In cases where the taxonomic iden�ty is unclear, BRS also refers to peerreviewed scien�fic literature or the latest standards used by scien�fic socie�es to determine the plant 

pest status of the modified microbes.

5. Some commenters have requested that BRS postpone the finaliza�on of the dra� guidance un�l it 

has consulted with more stakeholders. They also suggested revising the guide to be more in line with 

BRS' policy of making regulatory decisions based on scien�fic evidence.

Response: 

We agree that further coordina�on and clarifica�on must occur before BRS can finalize the guide. For 

this reason, BRS is pos�ng a second dra� version. We have also updated the guide to indicate that 

applicants can submit mul�-year (2-3 years) permit applica�ons for importa�on and interstate 

movement of modified microbes and can submit permit applica�ons for importa�on and interstate 

movement of bacteria and fungi at the genus level. Since 1987, APHIS has issued more than 5,200 

permits and acknowledged more than 14,000 no�fica�ons for interstate movement and importa�on 
5

ac�vi�es with modified organisms. Over this period, APHIS has rarely observed breaches in containment 

or accidental release of regulated material during shipment. Addi�onally, within APHIS, PPQ issues 

three-year permits for the importa�on and interstate movements of non-modified organisms, and the 

Preamble to the 2020 revision to APHIS’ biotechnology regula�ons specifically noted that the revised 

regula�ons allow mul�-year permits for modified organisms. Limi�ng permits for interstate movement 

and importa�on of modified organisms to one year had significantly burdened the regulated community. 

Developers had to submit repeated applica�ons to move material between loca�ons. Such ac�vi�es also 

placed a resource burden on BRS, when conduc�ng reviews and authorizing shipments every year, even 

though the regulated ac�vi�es had low-risk poten�al. Issuing mul�year permits for interstate movement 

and importa�on of modified plants, microbes, and insects reduces a significant burden for the regulated 

community and BRS, saving applicants �me and resources, and allowing for risk-propor�onate regula�on 

for this type of ac�vity. APHIS considers individual circumstances when deciding an appropriate dura�on 

for each permit. Applicants will be able to seek permit amendments to address changes in planned 

research.

BRS is also clarifying that species belonging to the same genus can be included within a single 

importa�on or interstate movement permit applica�on if containment protocols are appropriate for all 

species and they remain securely contained during shipment. BRS has previously issued permits for 

mul�ple species that share biological traits that enable similar containment protocols, and PPQ issues 

permits for mul�ple microbe species at higher taxonomic levels. BRS is limi�ng permit applica�ons to the 

genus level in order to facilitate �mely permit approval given the larger number of constructs that could 

be included in a permit applica�on for higher taxonomic levels and the �me it would take to review a 

larger applica�on. In the future, a�er BRS updates this dra� guide to further address comments from 

stakeholders on the Request for Informa�on associated with Execu�ve Order 14081, BRS will, at that 

�me, take addi�onal public comment. 

Comments regarding the need for beter coordina�on among regulatory agencies.

Commenters requested beter coordina�on among regulatory agencies to streamline the data 

requirements. They would like to see more communica�on between BRS and EPA to reduce confusion 

over which rules and regula�ons apply, par�cularly if there is conflic�ng informa�on. 

Response: 

As noted above, we agree that addi�onal coordina�on and clarifica�on would be helpful. Although we 

rou�nely meet with both PPQ and EPA, BRS will work with PPQ and EPA to streamline and align data

requirements where possible. To allow for this work to proceed, BRS is pos�ng this guide as a second 

dra� to support current applica�ons for permits and, in the future, will provide more clarity on 

informa�on requirements for permit applica�ons, among other things.

Comments about adding permit requirements for conduc�ng research in contained facili�es

1. Mul�ple commenters expressed the concern that a modified microbe does not require a BRS permit 

if the experiment for the microbe is conducted in a contained facility. These commenters opined that 

BRS should require permits for contained facili�es to prevent accidents and ensure facili�es are truly 

suitable for working with microbes, and to oversee novel microbes. 

Response: 

Under the Plant Protec�on Act, BRS has authority to regulate the importa�on, interstate movement, and 

release into the environment of certain modified microorganisms. 7 U.S.C. §§ 7711 and 7712. Ac�vi�es 
6

that do not fall within those categories – like research in structures that meet the criteria of a “contained 

facility” as defined in the regula�ons – fall outside of the scope of the Plant Protec�on Act and 7 CFR 

part 340. We appreciate the commenters’ concerns about ensuring the safety of research ac�vi�es in 

contained facili�es. When reviewing an applica�on for importa�on or interstate movement of a modified 

microbe, we ensure that the receiving facility is adequate to ensure containment of the microbe. In the 

guide, we explain that a BRS permit is not required if a developer is crea�ng a modified microbe and 

conduc�ng research ac�vi�es involving that modified microbe in an area mee�ng the defini�on of 

“contained facility” (that is, a “structure for the storage and/or propaga�on of living organisms designed 

with physical barriers capable of preven�ng the escape of the organisms”) without impor�ng the 

microbe or moving it interstate. To ensure a facility prevents the unauthorized release of a modified 

microbe, we provide developers with resources they can use to ensure containment appropriate for their 

microbes. If a developer is unsure whether their contained facility is adequate to prevent the escape of a 

modified microbe, we encourage them to apply for a permit so that we can assist them with assessing 

their facility and determining whether the facility meets the criteria for a “contained facility” or whether 

they require a permit. We suggest this approach to help developers mi�gate against noncompliance with 

the regula�ons resul�ng from the unauthorized, accidental, or inadvertent release of a modified microbe 

subject to 7 CFR part 340, which could result in enforcement ac�on, including the assessment of civil 

penal�es.

2. A commenter emphasized the importance of Standard Opera�ng Procedures (SOPs) when 

submi�ng a BRS permit through the APHIS eFile system. In addi�on to movement, the point of 

origin, and release condi�ons, the condi�ons under which the experiments should be performed 

should also be part of the SOPs.

Response:

The guide provides informa�on to permit applicants and holders on how to keep modified microbes 

contained and secure to prevent any unintended release or spread in the environment. The guide covers 

different containment condi�ons, we have incorporated a checklist for facility inspec�ons into the guide,

and we thoroughly review SOPs to ensure proper procedures are in place to maintain confinement and 

prevent unauthorized release or spread of modified microorganisms in the environment.

3. One commenter expressed concern regarding trial termina�on and procedures to effec�vely stop 

persistence of the modified microorganism in the environment. 

Response:

Trial termina�on is a specific term rela�ng to the release of modified microorganisms authorized under a

BRS permit. In the guide, we discussed trial termina�on to assist permit holders in understanding their 

obliga�on to terminate their trial in a way that prevents unauthorized release, spread, dispersal, and/or 

persistence of the modified microorganism in the environment.

Comments regarding why certain microbes are exempted from regula�ons.

1. One commentator requested clarifica�on of why we use the term “exemp�on” (rather than 

excep�on) when describing modified microbes that are registered with EPA and, thus, are not 

required to follow BRS’ permi�ng requirements. The commenter noted that microbial pes�cide 

labeling should not be a defining factor in determining movement in and outside the environment. 

Another commenter pointed out that that some organisms (for example, agrobacterium) are exempt 

from the permi�ng requirements in 7 CFR part 340, while others are not, and wanted to understand 

the basis for and scope of this exemp�on.
7 

Response: 

7 CFR 340.5(f) indicates a permit is not required for the movement of any GE microorganism product 

that is currently registered with the EPA as a microbial pes�cide, so long as the microorganism is not a 

plant pest as defined in § 340.3. Although BRS and EPA operate under different statutory authori�es, 

they consider similar factors when evalua�ng a modified microbe’s risk. Since EPA’s review includes areas 

of concern to BRS, BRS recognizes EPA’s review and registra�on of a microbial product to avoid 

redundant regula�on and allows the agencies to make the best use of limited resources. BRS used the 

term “exempt” from regula�on because the permi�ng requirements apply to microbial pes�cides unless 

the product is registered with EPA. If, for example, the microbial pes�cide was no longer registered with 

EPA, the developer would be subject to BRS’ permi�ng requirements for importa�on, interstate 

movement, and environmental release. For addi�onal informa�on on whether a modified microbe is 

subject to 7 CFR part 340, please visit our ques�ons and answer webpage

htps://www.aphis.usda.gov/aphis/ourfocus/biotechnology/guidance-documents/qa-table/brs-qa and 

filter by “microbes”. 

Regarding the request that we clarify the basis for the exemp�on for disarmed Agrobacterium species, 

historically, these bacteria have been regulated and required permits for their interstate movement due 

to their classifica�on as plant pests. However, disarmed Agrobacterium species lacking disease-causing 

ability have been used as a tool to modify organisms for several years now. The interstate movement of 

these disarmed Agrobacterium species has not resulted in the dissemina�on of plant pests within the 

United States, and the plant pest risk associated with them is very low. Moreover, there are safeguards in 

place that can effec�vely mi�gate those risks. Therefore, for the reasons men�oned above, the interstate 

movement of disarmed Agrobacterium species is exempt from permit requirements.

2. A commenter suggests that BRS make it clear that microorganisms used for biocontrol, which do not 

present any risk to plants, do not need a permit.

Response: 

The revised regula�ons require a permit for a modified microbe that is intended to control a plant pest 

and could pose a plant pest risk. The revised regula�ons do not require a permit for a biological control 

organism that does not pose a plant pest risk and is not a plant pest. As we noted in the preamble to the 

May 2020 final rule, “We agree with the first comment (i.e., that organisms and microorganisms used to 

control plant pests should not require regula�on if they are not plant pests themselves or do not pose a 

plant pest risk), and this rulemaking does not provide for the regula�on of biological control organisms if 

they are not plant pests themselves or do not pose a plant pest risk.”

Miscellaneous comments

1. A commenter stated that BRS overlooks the majority of gene edited microbes, including those 

created with CRISPR technology, which, according to the commenter, will likely produce the most 

diverse range of gene�cally modified microbes in the future. 

Response: 

The defini�on of “gene�c engineering” in 7 CFR part 340, includes genome edi�ng, and our risk 

assessment is based on the characteris�cs of the modified organisms (that is, whether the new trait 

could pose a plant pest risk). This is known as product-based regula�on. Under the revised regula�ons, 

BRS does not consider whether the microbe was modified using genome edi�ng or a different method of 

biotechnology when evalua�ng whether it is subject to the regula�ons. 
8

2. Some commenters expressed concern about how BRS verifies the informa�on provided in permit 

applica�ons.

Response:

When considering an applica�on for impor�ng, moving interstate, or releasing modified microorganisms, 

BRS carefully evaluates all provided informa�on. Once a permit is issued, we are confident that the

permit condi�ons and SOPs describing how the developer will meet the permi�ng condi�ons will 

prevent any unauthorized release or spread or persistence in the environment. Addi�onally, BRS 

conducts regular inspec�ons of the facili�es and field trials of permit holders to ensure that they are 

following the permit condi�ons and associated SOPs. 

3. A commenter recommended that BRS consider addi�onal informa�on, such as the iden�fica�on of 

the biological proper�es of a species, when conduc�ng a permit review to ensure organisms are

properly evaluated and to assess any poten�al nega�ve impact it may have on other organisms. 

Response: 

The guide outlines comprehensive data requirements that BRS considers when evalua�ng permit 

applica�ons. Permit applica�ons must include all the required technical informa�on before BRS

evaluates and issues a permit. Part of this evalua�on includes assessing the proper�es of all species 

listed in the permit applica�ons. Most of the microbial species listed in permits are well-known to BRS 

and within the research community. If a new species is listed in a permit, we work with the applicant to 

gather literature and ensure that the permit contains appropriate condi�ons to ensure the modified 

microorganism will not be released, spread, dispersed, or persist in the environment. 

4. A commenter has expressed concerns that the regulatory monitoring of modified microbes under 7 

CFR part 340, may not provide adequate environmental protec�ons and does not allow public

review and comment related to permit applica�ons, which limits stakeholders in voicing concerns 

about the release or introduc�on of modified microbes.

Response: 

BRS follows APHIS Na�onal Environmental Policy Act (NEPA) Implemen�ng Regula�ons (7 CFR part 372) 

when evalua�ng permit applica�ons and establishing permit condi�ons to ensure containment or 

confinement of a modified microbe. Modified microbes o�en share many of the same biological 

characteris�cs as those of well-known microbes that APHIS is familiar with, and BRS has experience 

establishing permit condi�ons that have successfully contained and confined modified microbes, 

confirmed through compliance inspec�ons. In most of these instances, an environmental assessment or 

environmental impact statement that is subject to public review and comment is not required under 

APHIS’ NEPA Implemen�ng Regula�ons. If a confined field release of modified organisms involves new 

species or organisms or novel modifica�ons that raise new issues, or the release is not confined, BRS will 

prepare an environmental assessment or an environmental impact statement for public review and 

comment.