Overview

On 18 April 2022, FDA published a draft guidance document explaining the agency’s proposed approach to evaluating the public health importance of non-listed food allergens.¹ The Federal Food Drug and Cosmetic Act (FFDCA) identifies nine major food allergens: milk, eggs, fish, crustacean shellfish, tree nuts, peanuts, wheat, soybeans, and (after 1 January 2023) sesame. However, the nine major food allergens do not represent all foods that people are allergic to or that cause food hypersensitivities.

Since the Food Allergen Labeling and Consumer Protection Act (FALCPA) was enacted in 2004 and identified the original “Big Eight” food allergens, FDA has received a handful of requests to evaluate a non-listed food as a “food allergen of public health importance” and establish regulatory requirements.² In this new draft guidance, FDA outlines its approach to how it would evaluate similar requests in the future.

FDA may choose to evaluate the public health importance of a non-listed allergen on its own or in response to a citizen petition. FDA notes that if an interested stakeholder wishes for FDA to evaluate the public health importance of a non-listed food allergen, they should submit a citizen petition identifying and evaluating the body of evidence applicable to each of the scientific factors discussed below, and provide additional labeling and production information, if appropriate. The draft guidance also includes a detailed background section explaining the current regulatory framework for allergens and includes a discussion of the lowest eliciting dose for an allergen. Notably, however, the draft guidance is merely establishing the framework and process that the agency plans to follow for future evaluations of non-listed food allergens; it does not identify the scientific or legal standards that would be applied (e.g., the actual prevalence in the population of the allergen or severity of the reactions).

This draft guidance is one of three allergen-specific draft guidance documents that FDA identified earlier this year as priority guidance topics.³ The other two potential guidance topics (related to Food Allergen Controls under the Preventive Controls for Human Food Rule and a Question and Answer regarding food allergens) and have not been published.

FDA’s Approach

The draft guidance explains that FDA will evaluate a non-listed food as a food allergen of public health importance on a case-by-case basis using the following approach:

1. Scientific factors

FDA identified four scientific factors of food allergies that the agency intends to consider when evaluating the public health importance of a food allergen:

• evidence of an immunoglobulin E antibody (IgE)-mediated allergy;
• prevalence;
• severity; and
• potency.

FDA states that these factors are consistent with a number of existing criteria and frameworks.⁴

FDA intends to evaluate the strength of different types of evidence for each of the four scientific factors on a “low-medium-high” scale, referred to as a GRADE system (“Grading of Recommendations Assessment, Development, and Evaluation”). FDA included a chart summarizing the type of evidence that it would consider “high” “medium” and “low” strength for each of the four factors.

2. Other information FDA may consider

Only after the first four factors are satisfied, FDA may also consider information relevant to the labeling and production of food containing the allergen, similar to the data and information the agency requested for sesame (prior to its addition to the FFDCA listing of major food allergens). Examples of this information include:

• prevalence of IgE-mediated food reactions attributed to exposure to food that is not disclosed on the label of food products,
• prevalence and amounts of the undisclosed food allergen in foods;
• characteristics of food products and food production practices;
• patient-centered studies or other patient-centered information; and
• data on clinically cross-reactive IgE-mediated food allergies, and whether such cross-reactivity would not be well-recognized in the U.S. allergic population.

3. Evaluating the strength of the evidence

FDA will assess each food or food protein on a case-by-case basis, although it generally expects that only food or food proteins with high or medium evidence will be considered allergens of public health importance. Furthermore, if there is no robust (i.e., high or medium) evidence for the first factor (evidence of IgE-mediated food allergy), FDA does not expect to consider the other factors. 

References

1 Draft Guidance for FDA Staff and Stakeholders: Evaluating the Public Health Importance of Food Allergens Other Than the Major Food Allergens Listed in the Federal Food, Drug, and Cosmetic Act (April 2021), https://www.fda.gov/regulatory-information/search-fda-guidance-documents/draft-guidance-fda-staff-and-stakeholders-evaluating-public-health-importance-food-allergens-other.

2 FDA has explained that the phrase “allergens of public health importance” is used in the scientific community to refer to priority allergens that are not one of the major food allergens identified in the FFDCA. See Draft Guidance: Voluntary Disclosure of Sesame as an Allergen: Guidance for Industry (November 2020) https://www.fda.gov/regulatory-information/search-fda-guidance-documents/draft-guidance-industry-voluntary-disclosure-sesame-allergen.

3 See FDA Foods Program Guidance Under Development (https://www.fda.gov/food/guidance-documents-regulatory-information-topic-food-and-dietary-supplements/foods-program-guidance-under-development).

4 See Appendix A of the Draft Guidance.