The US Food and Drug Administration (FDA) issued final guidance titled Foods Derived from Plants Produced Using Genome Editing (Genome-Edited Plants Guidance), describing the agency’s approach for evaluating the safety of foods derived from genome-edited plant varieties. The Genome-Edited Plants Guidance also describes two voluntary processes for developers to inform and engage with FDA regarding the steps taken to ensure the safety of foods from their genome-edited plant varieties.
Then: FDA’s Historical Regulatory Approach to Foods from New Plant Varieties
In 1992, FDA published Statement of Policy: Foods Derived from New Plant Varieties (NPV Policy), which described risk-based principles for ensuring the safety of foods from new plant varieties under the Federal Food, Drug, and Cosmetic Act (FDCA). In the NPV Policy, FDA explained that foods derived from genetically modified plant varieties are regulated by FDA using “an approach identical in principles to that applied to foods developed by traditional plant breeding.” Further, FDA clarified that “irrespective of the method by which” the foods were developed, it would regulate such foods and review safety concerns based upon the “objective characteristics of the food and the intended use of the food (or its components).”
Now: FDA’s Same Risk-Based Approach to Foods from Genome-Edited Plant Varieties
The Genome-Edited Plants Guidance reaffirms the 1992 NPV Policy that the risk-based principles applicable to foods from new plant varieties (NPVs) also apply to foods produced from genome-edited plant varieties. FDA recognizes that unintended changes can occur with all plant breeding techniques, but do not always result in a food safety concern. However, FDA expects that foods from some plants produced using genome-editing may require “additional molecular, chemical, and/or nutritional analyses,” especially where FDA has concerns about the safety or nutritional characteristics of the resulting food.
As related to food for animals, FDA emphasizes that because animal food derived from a single plant variety may constitute a significant portion of the animal’s diet or that an animal may be fed the same or similar type of diet for their entire lives, a change in nutrient or toxicant composition that might be considered insignificant for humans may be a very significant change for an animal. Thus, nutrient composition and availability in animal foods are important safety considerations for animal health.
As related to the potential allergenicity of food for people, FDA reiterates its concerns expressed in the NPV Policy about the possibility that a known food allergen could be transferred from one food source to another. FDA encourages developers of genome-edited plants to refer to its recommendations in a 2006 guidance when assessing the potential allergenicity of a new protein to induce an allergic response in humans. In the Genome-Edited Plants Guidance, FDA strongly recommends that developers consult FDA before (1) transferring genetic material from an organism known to produce food allergens into a different food source, (2) modifying an organism’s genetic material to produce proteins similar or identical to those from an organism known to produce food allergens, (3) attempting to change the levels of specific allergens in food crops subject to labeling under section 403(w) of the FDCA, or (4) adding to food a new protein for which potential allergenicity is not known.
Looking Ahead: Voluntary Pre-Market Engagement with FDA
FDA outlines two methods—pre-market consultations and pre-market marketings—through which developers of genome-edited plants may voluntarily inform FDA of the steps they have taken to ensure the safety of foods derived from these plants. The agency recognizes that while there is no FDA pre-market approval requirement for NPVs, historically, developers have voluntarily consulted the agency prior to marketing foods. As described below, FDA provides recommendations when assessing and selecting between the two methods.
Voluntary Pre-Market Consultations
Since 1994, FDA has operated a voluntary pre-market consultation program for foods from NPVs. FDA publishes NPV consultations between FDA and the developer, including links to FDA memoranda and letters with its determinations. There have been, over the years, less than 10 consultations per year, and many consultations are related to herbicide, pesticide, and insect resistance of crops.
FDA recommends a voluntary pre-market consultation for foods produced from genome-edited plants that may be more likely to raise food safety questions or regulatory considerations because the modifications have one or more of the characteristics identified in the Genome-Edited Plants Guidance.
For example, FDA strongly recommends a pre-market consultation for the following modifications to the genome-edited plants:
- Modifications to endogenous genes that create significant homology to a known allergen relevant to human health or a toxin relevant to human or animal health
- Modifications that cause a non-negligible increase in levels of potentially harmful components, including toxicants, allergens, anti-nutrients, and other components that can exhibit non-nutritive physiological effects on humans or animals
- 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
- Modifications that introduce (1) new genes and/or genetic elements that do not naturally occur in that species or (2) additional copies of endogenous genes that are retained in the genome once genome editing is complete
In particular, modifications that introduce new genes and/or genetic elements into the food supply may raise questions about whether the expressed protein or new substance would be an unapproved food additive. If it is a new food additive, it would require FDA pre-market approval for use in food.
Voluntary Pre-Market Meetings
FDA recommends a voluntary pre-market meeting for foods with none of the characteristics identified in the Genome-Edited Plants Guidance and that are less likely to raise food safety questions or regulatory considerations. During the meeting, developers should be prepared to describe the safety characteristics of the food and explain the steps they have taken to ensure that food from their new plant variety is safe. Though FDA intends to publish a list of voluntary pre-market meetings on its website, it is unclear whether FDA will publish the contents of the meetings or whether a company can choose to keep these meetings confidential. Whether meetings will provide sufficient benefit is unclear.
Key Takeaways
FDA explicitly recognizes that the agency, in conjunction with other regulatory agencies like the US Department of Agriculture’s Animal and Plant Health Inspection Service or the US Environmental Protection Agency, may regulate new plant varieties and products derived from them. However, the types of data and information required to address each agency’s safety issues may differ. Therefore, food manufacturers should consult FDA prior to marketing foods produced from genome-edited plant varieties to show that the food is safe and complies with the FDCA. As emphasized in FDA’s Genome-Edited Plants Guidance, developers have a legal obligation to market only safe and lawful foods; consulting FDA through either voluntary process can help developers ensure they are meeting these obligations.
The Genome-Edited Plants Guidance shows that FDA is staying abreast of innovations in the food industry. Though FDA is focused on regulating the objective characteristics of the food, rather than the method of development, food industry stakeholders developing foods from new genome-edited plants should evaluate their manufacturing processes to ensure there are no safety concerns that could impact the food supply chain. Developers should consider the recommendations in this guidance and align their work, including early engagement with FDA, to facilitate an efficient marketing process.
While the guidance is final, it is open for public comment. Should stakeholders wish to comment, comments may be submitted on the eRulemaking Program’s designated website.