FDA's New Guidance Confirms FDA Pathway to Market for Foods from Gene Edited Plants

On February 22, 2024, the U.S. Food and Drug Administration (FDA or Agency) Center for Food Safety and Applied Nutrition (CFSAN) and Center for Veterinary Medicine (CVM) issued final guidance titled “Foods Derived from Plants Produced Using Genome Editing” (Guidance) that provides FDA’s recommendations for ensuring the safety of human and animal foods that are derived from new plant varieties produced using genome editing (foods from GE plants).

The Guidance may provide a streamlined pathway to market for certain foods from GE plants. In this sense, it responds to the Biden administration’s 2022 “Executive Order on Advancing Biotechnology and Biomanufacturing Innovation,” which directed a “whole-of-government” approach to the advancement of economic activity derived from biotechnology and biomanufacturing, including a promise to clarify — and potentially simplify — regulatory pathways for such products.

Overview

The Guidance was issued almost seven years after FDA’s notice requesting input on factual information and data about foods from GE plants,¹ which could help inform FDA’s thinking for these specific products; that request reportedly generated 580 comments. Fundamentally, the Guidance confirms that FDA’s 1992 “Statement of Policy: Foods Derived from New Plant Varieties”²  (New Plant Variety policy) applies to human and animal foods from GE plants, with the added requirement for human foods under Section 403(w) of the Federal Food, Drug, and Cosmetic Act (FDCA) that the label of a food containing an ingredient that is, or a protein derived from, a “major food allergen” comply with the allergen labeling requirements as applicable.

At the same time, the Guidance represents a sharp change from the New Plant Variety policy because it introduces a second voluntary premarket notification pathway specifically for foods from GE plants, a “premarket meeting,” which requires less information than what is required for a premarket consultation. The net result is that developers of foods from GE plants are encouraged to engage with FDA either through a premarket consultation, as outlined in the New Plant Variety policy and currently conducted by FDA, or the newly introduced “premarket meeting” pathway. Both of these pathways are voluntary, and FDA strongly encourages engagement “to help identify the data and information most relevant to food safety or other concerns specific to food from the new variety” and to provide FDA “with an awareness of the genome-edited plant products potentially on the market.” FDA also repeatedly reminds stakeholders that while these pathways are voluntary, statutory food safety requirements under FDCA Sections 402 and 409 apply to any human or animal food introduced into the market.

Risk-Based Choice of Voluntary Premarket Notification Pathway

According to the Guidance, the pathway choice is risk-based. Thus, if the food from a GE plant introduces certain traits or changes, FDA encourages a voluntary premarket consultation. Alternatively, if the food from a GE plant does not raise safety risks, FDA urges the developer to instead engage in a premarket meeting.

Premarket Consultation

It appears that FDA, more than 30 years after instituting the New Plant Variety policy, has now crystallized its key concerns based on its experience and increased understanding of the potential changes enabled by genetic engineering and genome editing. Thus, even while noting that the vast majority of New Plant Varieties “only very rarely” raise safety issues, the Guidance encourages innovators to engage in premarket consultation with FDA for issues of specific concern. Foremost of these is the potential allergenicity risk for foods from GE plants. Consistent with its April 2023 Letter to Industry on the Food Safety Risks of Transferring Genes for Proteins that are Food, FDA makes clear that developers that intend to transfer genes for proteins that are food allergens into new plant varieties must be acutely aware of safety risks as well as obligations of allergen labeling.

FDA states that premarket consultation is recommended for foods from GE plants that may have characteristics that warrant additional molecular, chemical, and/or nutritional analyses. FDA references its New Plant Variety policy as providing a tool to help developers identify safety risks but also includes a list of characteristics specifically developed to identify foods from GE plants that may raise safety questions or regulatory considerations, including “whether an added substance, such as a newly expressed substance resulting from genome editing, is an unapproved food additive.” That list includes plants that have been gene edited to contain

• modifications to endogenous genes that create significant homology to a known allergen
• modifications that cause a non-negligible increase in levels of potentially harmful components, including toxicants, allergens, and antinutrients
• modifications that can cause a non-negligible change in the level and/or bioavailability of a nutrient in a food
• modifications that change how the plant or food from the plant is used
• modifications that introduce (a) new genes and/or genetic elements that do not naturally occur in that species or (b) additional copies of endogenous genes that are retained in the edited genome 

The Guidance separately outlines specific safety considerations that apply to animal foods.

Premarket Meeting

The Guidance significantly abbreviates the voluntary regulatory process for notifying FDA about lower-risk foods from GE plants. This second pathway, a premarket meeting, is introduced as an alternative to the conventional premarket consultation and marks a noteworthy change in FDA policy. While CFSAN has long made itself available for premarket meetings to discuss products in development, the Agency has not previously formalized or created a public record of such meetings as an alternative to New Plant Variety consultations or in the context of Generally Recognized as Safe notices pursuant to 21 C.F.R. § 170.203 et seq.

A premarket meeting is designated as an alternative to premarket consultation appropriate for foods from GE plants that do not have any of the characteristics identified in the Guidance that may raise food safety questions. As such, a premarket meeting is intended to familiarize FDA with the types of foods from GE plants entering the market and the steps taken to ensure their safety. Critically, the premarket meeting does not require the level of information associated with a consultation and does not result in the same level of transparency. The Guidance simply states that a notice of the meeting will be posted on FDA’s website. It is not clear whether this new premarket meeting pathway is also available as an alternative for new plant varieties that do not involve gene editing of any kind.

Focus on Transparency

FDA’s move to streamline pathways to market differs somewhat from the U.S. Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) efforts to do the same with implementation of the 2020 Sustainable, Ecological, Consistent, Uniform, Responsible, Efficient (SECURE) Rule. Similar to FDA, the SECURE Rule takes a streamlined risk-based approach. However, to do so, the SECURE Rule exempts plants containing certain low-risk genetic modifications from any permit requirement; in such cases, the developer can introduce the plant without notifying APHIS.³ In contrast, while FDA also aims to streamline its regulatory approach for low-risk plants, it urges developers to notify the Agency — through either premarket consultation or meeting — that it plans to introduce food from a GE plant. FDA explains that such transparency helps to “foster public confidence and transparency in the use of such technologies.”

Questions Remain

Still, questions remain. The Guidance is final, but FDA states that it will accept electronic or written comments at any time.

Stakeholders should consider asking FDA for clarification on the scope and type of information that would be part of a premarket meeting and how such information would be shared publicly. It would also be worth knowing whether FDA intends to make the premarket meeting pathway available for foods from new plant varieties that do not utilize gene editing. And finally, it would be helpful to understand whether either premarket notification pathway would generate an FDA response reflecting the extent to which the Agency has considered the product, which can be helpful in industry communications.

¹ 82 Fed. Reg. 6564 (Jan. 19, 2017).
² 57 Fed. Reg. 22984 (May 29, 1992).
³ See 85 Fed. Reg. 29790 (May 18, 2020).