Millions of Americans have allergic reactions to food every year. While most food allergies cause relatively mild and minor symptoms, some food allergies may provoke reactions that are life-threatening. There is no cure for food allergies, so strict avoidance of food allergens is an important measure to prevent serious health consequences. The Food and Drug Administration (FDA) is responsible for the safety of the food supply for Americans, including those consumers with food allergies.
An allergic reaction to food occurs when the body’s immune system mounts a strong, rapid response to a specific food protein to which the body has become sensitized. Consumption of the food protein may trigger the immune system’s sudden release of histamine and other immediate-release chemicals, resulting in an allergic reaction. The reaction may be mild, resulting in a rash, hives, itching, or swelling or; the reaction may be sudden and severe, causing troubled breathing, wheezing, loss of consciousness, and potentially, death. Scientists estimate that as many as 15 million Americans suffer from food allergies. Although some people have a diminished response to food allergies as they mature, there is currently no cure for food allergy; consumers that have allergic reactions to certain foods must use avoidance to prevent allergic reactions.
Eight foods account for 90 percent of all food-allergic reactions. They are milk, egg, peanut, tree nuts (e.g., almonds, pecans, walnuts), fish (e.g., bass, cod, flounder), Crustacean shellfish (e.g., crab, lobster, shrimp), soybeans and wheat. Some people may outgrow the allergic response to certain allergens, but others will remain allergic to certain foods for life.1 These eight foods have been defined as major food allergens in the Food Allergen Labeling and Consumer Protection Act (FALCPA) of 2004. FALCPA also stated that food regulated under the Food, Drug and Cosmetic Act are misbranded unless they declare the presence of major food allergens on the product label, using the common or usual name of the major food allergen, as allergic consumers must use avoidance to prevent allergic reactions. Excluded from the definition is any highly refined oil derived from a major allergic food (such as peanut or soy) and any ingredient derived from the highly refined oil.
FDA established a Federal Register docket in December of 20122 to obtain comments on the information necessary to conduct a risk assessment to establish regulatory thresholds for the major food allergens. The comment period for collecting information on developing allergen thresholds has been extended, with the agency accepting comments through May 13, 2013.3 There are two mechanisms outlined in FALCPA through which ingredients may be deemed to be exempt from the major food allergen labeling requirement. First, an individual may petition for exemption by providing scientific evidence that the ingredient “does not cause an allergic response that poses a risk to human health.”4 Alternatively, a notification may be submitted that either provides scientific evidence showing that an ingredient does not contain allergenic protein, or that, through the premarket approval process, a determination has been made that the ingredients “does not cause an allergic response that poses a risk to human health.”5 FDA is now working to establish a regulatory threshold (or action level) for the major food allergens, to help FDA “determine whether, or what type of, enforcement action is appropriate when specific problems are identified” as well as to help establish a standard for evaluating claims that have been put forth in FALCPA petitions that an ingredient “does not cause an allergic response that poses a risk to human health” or “does not contain allergenic protein.” FDA also believes that regulatory thresholds would also help in the conducting of hazard analyses and in the development of standards for allergen preventive controls in the food industry.
FDA had previously established a Threshold Working Group that determined in 2006 that a quantitative risk assessment-based approach is the “strongest, most transparent” approach to establishing thresholds for food allergens. The Working Group also stated that the quantitative approach provided the best ability to evaluate both the level of protection and the degree of uncertainty associated with a food allergen exposure level. However, the Working Group acknowledged that additional clinical and epidemiological data were needed to develop appropriate risk assessment tools and to support a quantitative risk assessment.
FDA opened the docket2 to determine if current scientific advances in food allergen-related identification methodology and data resources are sufficient to support a quantitative risk assessment and if so, to use the appropriate data and tools to evaluate the public health impact of establishing specific regulatory thresholds for one or more of the major food allergens. The discussion of food allergy thresholds is not confined to the U.S., as a workshop on this subject was held in Denmark in 20126 in which a consensus was reached to first derive action levels from currently available data, which would include proposing a tolerable level of risk to the allergic population, and to also perform a “one-dose” clinical trial (with a low challenge dose) in multiple centers in order to better understand the applicability of dose-distribution models and help validate the threshold levels previously derived. In 2002, Japan instituted a threshold level of 10 parts per million (ppm)7, while in Switzerland known allergenic foods contained in a food product at greater than 1000 ppm must be declared as ingredients since 1999.
There are several scientific aspects that must be kept in mind when evaluating the applicability of the determination of allergen threshold levels in foods. In general, the severity of an allergenic reaction for any one individual is assumed to be proportional to the level of intake of the food protein and that individual’s degree of sensitization to that food protein.8 There has also been a general belief that there is a “threshold” level below which a sensitized person would not likely react to an allergenic food protein. However, clinical data indicate that the threshold dose level can vary from person to person, and the threshold level can even change within a single individual over time.
Most information concerning allergenic thresholds has been obtained through clinical trials, and the responses to the different food allergens have been variable. Eller et al. (2012) found that in a clinical trial to compare clinical threshold values for egg, hazelnut, milk and peanuts, and in trying to correlate these threshold responses to the severity of symptoms, the thresholds for the different foods were not comparable, and the dose necessary to elicit an allergic response was different for the four different foods, even when adjusted for protein content.
In addition to the ability to accurately detect allergic responses in clinical trials, a significant aspect of the allergen threshold concept is the ability to develop the necessary analytical procedures to accurately identify allergenic proteins in a quantitative fashion. Health Canada has been working to define specific criteria for allergen methodology and validate quantitative ELISA methods for the determination of food allergens, utilizing eggs and milk as example allergens. Some data indicate that methods to detect food allergen proteins must have a sensitivity of greater than 10 ppm, although definitive guidance from the FDA on which protein fractions of each of the major food allergens must be measured has yet to be completed. Japan has instituted the use of quantitative ELISA methodology as a screening test, with qualitative confirmation tests using Western blotting or polymerase chain reactions (PCR), and guidance drafted by the Japanese government may be helpful in the composition of guidance by FDA.10
FDA, in concert with other regulatory bodies, is working to advance the ability to utilize food allergen threshold levels for foods by evaluating the current clinical and analytical information to determine the impact of establishing threshold levels on the health of individuals with food allergies.
Federal Register, Vol. 77, No. 241; 74485 – 74486. December 14, 2012.
Federal Register, Vol. 78, No. 23; 7785-7786. February 4, 2013.
21 U.S.C. 403(w)(6)(C).
21 U.S.C. 403(w)(7)(C).
Madsen et al., 2012.
eu-vital.org/en/declaration.html; site last visited March 6, 2013.
Taylor et al., 2009.
Abbott et al., 2010.
Sakai et al., 2012.