On February 22, 2024, FDA released a final guidance[1] detailing how foods derived from genome-edited plants fall into FDA’s existing food safety framework and outlining two voluntary consultation processes for developers.

The new guidance applies FDA’s 1992 policy regarding Foods Derived from New Plant Varieties (“NPV policy”) to foods derived from GE plants, consistent with the approach taken in FDA’s 1997 guidance describing the NPV policy’s associated consultation procedures. Overall, FDA concluded that “the risk-based principles laid out in the NPV policy” are sufficiently flexible to accommodate foods derived from modern genome-edited plants.

The 2024 guidance outlines two voluntary premarket procedures that FDA will offer to industry moving forward: the pre-existing voluntary premarket consultation process and a new “simple meeting” option for foods derived from GE plants that meet certain qualifications, discussed below. While the consultation programs are technically voluntary, FDA reminded the industry that “developers are responsible for ensuring that plant-derived human and animal foods are safe and comply with all applicable legal and regulatory requirements” that fall under FDA’s purview. These consultations provide a pathway to market with FDA’s input on key regulatory questions.

The guidance follows the Biden administration’s push to clarify the regulation of products derived from genome editing techniques as part of the National Strategy for Modernizing the Regulatory System for Biotechnology and reflects FDA’s experience with 200 voluntary premarket consultations and input from more than 500 comments received from FDA’s 2017 Request for Information on the topic.

New Plant Varieties (NPV) Policy

In 1992, long before modern genome editing techniques such as CRISPR and TALENs became commonplace, FDA issued a policy statement on foods derived from new plant varieties (which became known as the “NPV policy”) in response to stakeholder inquiries regarding recombinant (e.g., transgenic) DNA technology, which, at the time, was the state of the art. Under the 1992 NPV policy, foods derived from such technology are regulated within the pre-existing food safety framework and on equal terms with foods derived from plants developed by traditional plant breeding. The 1992 NPV policy was to regulate foods derived from new plant varieties “irrespective of the method by which it is developed” and instead based on “objective characteristics of the food and the intended use of the food (or its components).”

The 2024 guidance continues to extend this policy to the products of modern genome editing technologies, which are more precise and more efficient than the technology available in 1992. The guidance reiterates the product-over-process approach to regulating the products of genome editing. However, FDA explains that foods derived from GE plants may face higher scrutiny in some respects, depending on the modified trait(s). For example, FDA may “expect” “additional molecular, chemical, and/or nutritional analyses” for some foods, such as “those that contain new proteins that raise toxicological or allergenicity questions, produce substances that have not normally occurred in that food, have an increased/decreased level of a substance typically found in that food, and/or have modified nutritional content.”

FDA raised specific safety concerns about the potential for food allergens to be transferred from one food source to another or new proteins in food to induce an allergic response in humans. FDA recommended consulting FDA before “(1) transferring genetic material from an organism known to produce food allergens into a different food source, (2) modifying the genetic material of an organism to produce proteins similar or identical to those form an organism known to produce food allergens; (3) attempting to change the levels of specific allergens in crops producing foods subject to [allergen labeling requirements under 403(w) of the Federal Food, Drug & Cosmetic Act]; and (4) adding to food a new protein whose potential allergenicity is not known.

Voluntary Premarket Processes

The new guidance also summarizes FDA’s two voluntary premarket processes available for producers of foods derived from new plant varieties produced using genome editing—premarket consultations and premarket meetings, the latter of which is new—and provides its recommendations for how to choose between them. Although both processes are indeed technically voluntary, developers of genome-edited plants from which foods could be produced often favor early and active engagement with FDA.

1. Premarket consultation

A science-based, case-by-case approach to food safety assessment, offered since 1994, that considers the objective characteristics of the food and its similarity to foods that have been safely consumed.

FDA strongly recommends a premarket consultation if the genome-edited plant includes:

• Modifications to endogenous genes that create significant homology to a known human allergen or a toxin that is relevant to human or animal health;
• Modifications that cause a non-negligible increase in levels of potentially harmful components, such as toxicants, allergens, and anti-nutrients;
• Modifications that cause a non-negligible change in the nutritional value of the food;
• Modifications that change how the plant or food from the plant is used; or
• 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 genome once genome editing is complete.

2. Premarket meeting

A new, informal consultation between developers and FDA before marketing food from biotechnology-derived plant varieties that may not require an intense review.

FDA recommends a premarket meeting if the genome-edited plant does not include the above-listed modifications.

The guidance encourages developers to meet with FDA early and as often as necessary and emphasizes that developers with limited regulatory experience may find engagement with FDA especially beneficial. More information on how FDA regulates new plant varieties can be found on FDA’s website.

U.S. Coordinated Framework for Biotechnology Products

The guidance reminds developers that genome-edited plants and other products of biotechnology are regulated in the U.S. by the Coordinated Framework, and that compliance with FDA’s food safety laws does not imply compliance with other regulations enforced by other agencies (e.g., the U.S. Department of Agriculture (USDA) and the U.S. Environmental Protection Agency (EPA)). For recent updates on how EPA and USDA regulate gene-edited plants, please see our recent blog post and subscribe to MoFo Life Sciences for the latest insights on biotechnology regulation and policy.

[1] Staff from FDA’s Office of Policy informed Morrison Foerster via phone call that the guidance was issued as a Level 2 guidance document. Per FDA’s Good Guidance Practices website, Level 2 guidance documents are issued without prior public comment and “address existing practices or minor changes in FDA’s interpretation or policy.”

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