EPA Provides Draft Guidance for Regulation of Gene Edited PlantsSeptember 4, 2020

Background

Although the USDA gets the most attention related to the regulation of gene edited plants, in the United States products of biotechnology are regulated by the USDA, FDA and EPA under the Coordinated Framework for the Regulation of Biotechnology, updated most recently in 2017.

Under this framework, the USDA, FDA and EPA each regulate in accordance with their specific laws and regulations.

EPA regulates genetically engineered plants which contain plant incorporated protectants (PIPs).  PIPs are defined at 40 CFR § 174.3 as “a pesticidal substance that is intended to be produced and used in a living plant, or in the produce thereof, and the genetic material necessary for the production of such a pesticidal substance”. The term “pesticide” as defined in FIFRA 2(u) means (1) any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest, (2) any substance or mixture of substances intended for use as a plant regulator, defoliant, or desiccant, and (3) any nitrogen stabilizer.  EPA regulates pesticides under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA; 7 U.S.C. § 136), and establishes the amount of pesticide residues that may be present in food in accordance with section 408 of the Federal Food, Drug and Cosmetic Act (FFDCA; U.S.C. § 9).

Traditionally, PIPs are thought of as plants expressing a protein which confers pest resistance, such as Bt corn. However, note that pest resistance is broader than insect control and includes disease resistance as well, and that growth regulators and nitrogen stabilizers are also considered PIPs under the statute and supporting regulations. In addition, PIPs can also include traits that result from the loss-of-function of an existing plant gene where, for example, the inactivation of a gene coding for a receptor protein confers disease resistance.

Developers have been awaiting clear guidance from the EPA on what the regulatory approval process may look like for gene edited plants considered to contain plant incorporated protectants (PIPs). The EPA recently released a pre-publication version of their proposed rule regarding regulation of gene edited plants which contain PIPs, and provides for an exemption from some requirements under FIFRA if certain criteria apply. Once officially published, the EPA’s proposed rule will enter a public comment period for 60 days.

What does the proposed exemption mean?

The proposed exemption does NOT mean that the plants and plant products are not subject to regulation by the EPA; but this new rule would remove some requirements such as a pre-market pesticide approval under FIFRA, and provide a tolerance exemption under the FFDCA, for PIPs which meet the proposed exemption criteria.

Note that if a plant product meets this exemption, developers are still required under FIFRA to meet the adverse effects reporting requirement at 40 CFR § 174.71 and proposed recordkeeping requirements at 40 CFR § 174.73, which include a requirement to maintain documents supporting the determination of exempt status.

Plants with plant incorporated protectants that do not qualify for the exemption under this proposed rule are subject to all the requirements of FIFRA, including permit requirements and a pre-market approval from EPA.

What are the requirements for exemption?

EPA currently exempts PIPs produced through conventional breeding from sexually compatible plants as described in 40 CFR § 174.25. Because the EPA had previously defined sexually compatible plants as including only those plants that create viable progeny through conventional breeding, the current exemption excludes PIPs created through biotechnology, even if they are equivalent to PIPs that could have been developed through conventional breeding.

EPA’s proposed rule allows exemption for PIPs created through biotechnology in which the pesticidal substance is found in plants that are sexually compatible with the engineered plant, where specific safety criteria are met. A high-level summary of the two routes are below.

To qualify for the exemption, there are 2 pathways:

1. Pesticidal substance from a plant-incorporated protectant comes from a sexually compatible plant created through conventional breeding.

This is an edit to the existing exemption for plants produced through conventional breeding, to add section (c) which explicitly clarifies that the genetic material is only transferred via conventional breeding. The exemption applies if the following conditions are met:

a. (Existing) The genetic material that encodes thepesticidal substance or leads to the production of the pesticidal substance is from a plant that is sexually compatible with the recipient plant.

b. (Existing) The genetic material has never been derived from a source that is not sexually compatible with the recipient plant.

c. (New) The genetic material is transferred from the source plant to the recipient plant only through conventional breeding.

In addition, residues of the pesticidal substance from such plants created through conventional breeding are exempt from the requirement of a tolerance, if the residues of the pesticidal substance are not present in food from the plant at levels that are injurious or deleterious to human health.

2. Pesticidal substance from a plant-incorporated protectant based on a sexually compatible plant created through biotechnology.

The pesticidal substance from a plant-incorporated protectant based on a sexually compatible plant created through biotechnology is exempt from certain FIFRA requirements if all of the following conditions are met:

(a) The pesticidal substance is created through biotechnology from either an insertion of new genetic material as discussed in paragraph (a)(1) or a modification of existing genetic material as discussed in paragraph (a)(2).

(1) A native gene is engineered into a non-genic location of the recipient plant genome, resulting in a pesticidal substance identical to the pesticidal substance identified in the source plant.

(2)(i) The existing native gene in the recipient plant is modified to alter the amount of pesticidal substance produced without altering the identity of the pesticidal substance produced; or

(ii) The genetic material that encodes the substance of the existing native gene is modified to result in a pesticidal substance that is identical to the pesticidal substance encoded by a native allele of that gene; or

(iii) The existing genetic material is modified pursuant to both (i) and (ii).

(iv) The existing native gene in the recipient plant is modified to lose function through the reduction or elimination of the substance encoded by that gene.

(b) The pesticidal substance is not expressed at higher levels, in different tissues, or at different developmental stages than identified in a plant that is sexually compatible with the recipient plant.

For the residues of a pesticidal substances from such a plant produced by biotechnology to be exempt from the requirement of a tolerance, the following requirement also applies:

The residues of the pesticidal substance are present only in tissues and developmental stages identified in a plant that is sexually compatible with the recipient food plant, and do not exceed levels found within that plant, as long as those levels are not injurious or deleterious to human health.

Importantly, note that any ingredients intentionally added during the development of PIPs created through biotechnology that are specific to the production of the active ingredient (e.g., guide RNA, DNA nuclease) would need to be either be transiently transformed or would need to be removed through segregation of the trait during the breeding process, to meet the exemption criteria.

What is the process for obtaining exemption status?

The proposed rule includes a process for developers of PIPs to submit either a self-determination letter, or request for EPA confirmation that their PIP meets the criteria for exemption. Developers can also submit both the self-determination letter along with a request confirmation from the EPA.

Conclusion

Gene edited plants which are considered PIPs are subject to regulation by the EPA.  This newly proposed rule provides a path for exemption from some FIFRA requirements if certain criteria are met: namely, that the plant is produced through conventional breeding, or that biotechnology is used to engineer a native gene into the recipient plant or modify an existing native gene in a particular manner. After implementation, the rule in final form will certainly shape product development and regulatory strategy decisions, as the requirement to seek a full EPA approval comes with substantial time and financial implications.

For information on the interplay between this proposed rule and exemptions for gene edited plants under the new USDA SECURE Rule and Plant Protection Act, or for guidance on specific genetic changes and the potential application of exemptions under this proposed rule and potential regulatory strategy, please contact Cassie Edgar.

Cassie J. Edgar, Patent Attorney and Chair of the Regulatory Law practice group, advises clients in intellectual property, regulatory law, crisis management, compliance, stewardship, lobbying, and matters with USDA, FDA, EPA, and FTC. For additional information, please visit MVS or contact Cassie directly via email at cassie.edgar@ipmvs.com.