allergens

By Laurie Post, Ph.D.

On May 16, 2023, FDA released a draft compliance policy guide (CPG) that provides guidance for FDA staff, including investigators, on FDA’s enforcement policy regarding major food allergen labeling and cross-contact. While FDA guidance documents should be reviewed as recommendations, unless specific regulatory or statutory requirements are cited, these type of communications from the FDA are useful to industry because they present FDA’s current thinking and polices on significant food safety topics. The current draft CPG updates the 2005 CPG Sec 555.250 Statement of Policy for Labeling and Preventing Cross-contact of Common Food Allergens. The recent draft CPG provides a more detailed perspective on FDA’s current policies on food allergen labeling requirements, allergen cross-contact, voluntary allergen information (e.g., advisory label statements), thresholds, and regulatory actions. FDA states that their regulatory approach in addressing allergen violations will be case-by-case and dependent on the facts of each situation.

Allergen Cross-Contact and FDA’s Regulatory Approach

Allergen cross-contact is the unintentional incorporation of a food allergen into a food that does not contain that allergen as an ingredient. It is defined in FDA’s rule titled, “Current Good Manufacturing Practice, Hazard Analysis, and Risk-Based Preventive Controls for Human Food” 21 CFR part 117.

Allergen cross-contact may occur due to practices such as failure to adequately clean shared equipment, failure to properly segregate allergens, improper rework addition, or improper production scheduling. The draft CPG notes that the likelihood an allergen will be present due to cross-contact can be impacted by factors such as the characteristics of the food, the distribution of the allergen within a food (homogeneous versus particulate), the type of manufacturing process, the equipment used, and the cleaning procedures applied (e.g., dry cleaning versus wet cleaning).

While FDA acknowledges the factors that lead to allergen cross-contact, the draft CPG also confirms FDA’s position that “major food allergens unintentionally incorporated into a food are not to be declared in the ingredient list or the ‘Contains’ statement.” Manufacturers must instead comply with applicable requirements to address the potential for allergen cross-contact through appropriate preventive controls established in 21 CFR Part 117. With a few exceptions, these preventive controls requirements specify that food facilities must implement a food safety plan that includes a hazard analysis to identify known or reasonably foreseeable hazards that require a preventive control and must significantly minimize or prevent allergen hazards so that the food product will not be adulterated (section 402 of the FD&C Act (21 U.S.C. 342(a)) or misbranded (section 403(w) of the FD&C Act (21 U.S.C. 343(w) (21 CFR 117.135).

FDA generally regards a product to be misbranded when case-by-case review of the evidence shows that the product’s label bears incomplete or inconsistent product information regarding major food allergens.

• The food is formulated to contain a major food allergen as an ingredient and fails to declare on the label the major food allergen in either the ingredient list or the “Contains” statement as required (section 403(w) of the FD&C Act (21 U.S.C. 343(w)).
• The food is fabricated from two or more ingredients but fails to declare on the label the common or usual name of the ingredient in the ingredient list as required (section 403(i)(2) of the FD&C Act (21 U.S.C. 343(i)(2)).

FDA generally regards a product to be adulterated when a case-by-case review of the evidence, including inspectional evidence or other information, demonstrates that allergen cross-contact may render the product injurious to health (section 402(a)(4) of the FD&C Act (21 U.S.C. 342(a)(4)).

• When there is evidence of inadequate allergen cross-contact controls, FDA may deem a product adulterated even when the product bears an allergen advisory statement.

For example, inadequate sanitation control, such as failure to adequately clean shared equipment between production runs of products with different allergen profiles, may render the product adulterated. As another example, inadequate allergen label controls, such as failure to check the product label to ensure major food allergen ingredients intended to be in the food are labeled as required, may result in a misbranded product.

If testing detects an allergen in food or FDA suspects an allergen is present because of one or more adverse consumer reactions, but the origin of the allergen in the product is not known, FDA may follow up with the company to obtain additional information such as product formulation, ingredient information, and information about other products made on the same line or in the same process environment.

When analytical test results are available that establish presence of an allergen not intentionally added to the food, the draft CPG directs investigators to consult with the CFSAN/Office of Compliance on the health hazard posed by the product to determine whether the product is adulterated. A case-by-case evaluation of the allergen health hazard will include factors such as estimated exposure to unintended allergen presence per eating occasion, likelihood of product consumption by allergic consumers, any mitigating allergen information on the product, and other evidence such as evidence of insanitary practices, type of allergen control problem resulting in cross-contact, characteristics of allergen residues due cross-contact (e.g., particulates, dusts, etc.), and consumer adverse reactions.

The draft CPG explains that if there is a reasonable likelihood of serious adverse health consequences or death due to allergen misbranding or adulteration, FDA may consider immediate action to remove the food from commerce. If the company does not initiate a voluntary recall, FDA will consider other appropriate actions, such as mandatory recall, administrative detention, and/or suspension of facility registration.

Voluntary Allergen Information
FDA notes that allergen advisory statements such as “may contain [allergen]” may be used to alert consumers to the possible presence of a major food allergen due to cross-contact. They do, however, explicitly state that advisory statements are not a substitute for adherence to CGMPs and preventive controls. In a footnote, FDA states that the “presence of allergen advisory statements may be considered a health risk mitigating factor when allergen cross-contact is appropriately managed consistent with CGMPs, preventive controls, or other controls (e.g., HACCP).” This is a rare instance where FDA publicly acknowledges that advisory statements may be appropriate in certain circumstances. However, FDA also
notes that consumer adverse reactions may provide some evidence that labeling information or other factors did not effectively mitigate health risk from exposure to the allergen hazard in the product. The draft CPG also discusses the use of allergen-free claims and notes that such claims must be truthful and not misleading. FDA states expressly that if a product is labeled “milk-free,” the product should contain no milk allergen in the product. The draft CPG does not detail what controls or processes, e.g., final product testing, are needed to substantiate allergen-free claims.

Thresholds
FDA states in the draft CPG that it has not established a threshold for any major food allergen, but notes
that it is aware of published dose response data that raises the possibility that certain low-level exposure
to allergens “may not pose a health hazard to the majority of food allergic individuals.”
FDA states that where analytical test results are available when making the health hazard determination
discussed above, it will consider the estimated exposure per eating occasion to the allergen in that food.
However, FDA would also have to consider the allergenicity threshold (i.e., the maximum amount of
allergenic food that can be tolerated) of the particular allergic population consuming the product. While not explicit, this appears to indicate that FDA will take into account threshold information on a case-bycase basis when considering whether a product is adulterated due to cross-contact.

Comment Period
FDA asks for comments on the draft CPG by July 17, 2023, although the agency accepts comments on
guidance documents at any time.