A Conversation with Stefano Luccioli, M.D.
Food allergies are a complex public health problem impacting millions of Americans and their families. To help protect consumers with food allergies, the U.S. Food and Drug Administration (FDA) enforces laws that require listing of ingredients used in packaged food products so that consumers can find ingredients they are allergic or sensitive to in a food. In addition, foods or ingredients from major food allergens must be listed clearly by source on the label of packaged foods --for example “flour (wheat).”
The challenge for food allergic consumers and their caregivers navigating food options is not limited to store-bought products. Whether at restaurants or in the homes of relatives or friends, people who are allergic to certain foods must remain vigilant, since exposure to food allergens poses a risk for potentially severe and life-threatening reactions, says Dr. Stefano Luccioli, a medical officer and allergy specialist in the FDA’s Center for Food Safety and Applied Nutrition.
What drives Dr. Luccioli’s work is ensuring that allergen hazards are identified and controlled in the food supply. This also includes gaining a better understanding of the risk for reactions from food allergen exposure and finding ways to control and communicate this risk to improve the quality of life for allergic consumers. Here, he shares his insights about the current food allergen landscape and emerging research that may change the way we think about, and live with, food allergies.
Q: Why is food allergy a complex problem?
A number of commonly consumed foods are food allergens, and they are abundant in the food supply. They can be in a variety of ingredients and products, and even small amounts can cause reactions in allergic people.
If an FDA-regulated packaged food product contains an ingredient that is one of the eight major food allergens—peanuts, shellfish, tree nuts, milk, eggs, fish, soy or wheat—or any ingredient derived from these foods, it is required to be identified on the label. An example of an ingredient derived from these foods is whey from milk. On April 23, 2021, the Food Allergy Safety, Treatment, Education, and Research (FASTER) Act was signed into law, declaring sesame as the 9th major food allergen recognized by the United States. This change will become effective on January 1, 2023, so labeling of sesame as an allergen will not be required until that time.
The eight major food allergens were selected because, at the time the Food Allergen Labeling and Consumer Protection Act of 2004 (FALCPA) was passed, they were responsible for 90 percent of food allergies and thus were the most common causes of severe food reactions in the United States. But they didn’t then and don’t currently represent all foods worldwide that people are allergic to, which includes more than 160 foods. In some other countries, for example, mustard, lupin, and celery are also identified as priority allergens for labeling purposes.
In addition, while current FDA labeling laws require foods other than major food allergens to be included in the ingredient list when used as ingredients in food products, there are exceptions. A food that is not a major food allergen can be added to a food product without declaring the specific name in the ingredient list if it is a spice, color, or flavoring. For example, sesame can be included in “flavors” and “spices” and therefore sometimes not listed specifically on labels. Also, ingredients that are not a major food allergen can be labeled using the common or usual name of the food, which may not disclose the specific food source. For example, the common or usual name “tahini” (which is made from ground sesame seeds) does not specify sesame, unless it is labeled voluntarily by the manufacturer. The FDA recently released a draft guidance document asking manufacturers to voluntarily include the word sesame in labeling anytime it is used in a product. The guidance is intended to help protect consumers who are allergic to sesame by encouraging manufacturers to identify all ingredients that contain sesame right now. FDA continues to evaluate the emerging evidence and is working to develop factors to inform future regulatory actions related to other emerging food allergens, including possible labeling requirements.
Q: But when it comes to the eight major food allergens, can you be sure that it’s not in the food if it’s not on the label?
For the most part, yes, but there are instances when there may be inadvertent introduction of a major food allergen into a food product not intended to contain it. This is known as allergen cross-contact. Allergen cross-contact can happen in cases when there is shared food-processing equipment that may transfer an allergen to a product that shouldn’t contain it. For example, a manufacturer may use the same equipment to make both milk chocolate and dark chocolate, and the facility’s cleaning practices may not be adequate to remove all the milk protein on their equipment between the different batches.
There may also be instances of labeling or manufacturing errors that result in the presence of an allergen in product that is not properly labeled. Recalls due to undeclared food allergens are a leading cause of all food product recalls.
To address allergen cross-contact and other potential labeling or manufacturing errors leading to undeclared allergen hazards, FDA enforces laws and regulations applicable to food allergens. For example, under the Current Good Manufacturing Practice, Hazard Analysis, and Risk-Based Preventive Controls for Human Food rule, food manufacturers are required to implement controls to ensure accurate labeling of finished foods with respect to the major food allergens and controls to significantly minimize or prevent allergen cross-contact.
Q: How common is allergen cross-contact and what are the risks?
The likelihood of allergen cross-contact depends a lot on the type of product, type of allergen, and the processes the manufacturer uses. What the FDA has said is that if there is a possibility of allergen cross-contact, manufacturers should do everything possible to eliminate or significantly minimize this. Voluntary allergen advisory statements, also known as precautionary allergen labeling, like “may contain (allergen)” or “produced in a facility with (allergen),” have been used by food manufacturers to alert consumers about the possible presence of allergens due to allergen cross-contact.
Another potential concern with allergen cross-contact is that the level of allergen that may pose a risk for allergic consumers varies. While allergen advisory statements are often used, consumers should be aware that these statements are voluntary and there is no uniform rule that governs what they mean. Thus, a “produced in a facility” statement is not necessarily different from a “may contain” statement with regards to whether allergen cross-contact is more likely, or allergen presence is higher and poses greater risk. Indeed, many studies, including a 2013-2014 FDA survey on dark chocolate products, have consistently shown that the type of advisory statement does not correlate with presence or absence of allergen in the product or with allergen levels. For this reason, the Guidelines for the Diagnosis and Management of Food Allergy in the United States, developed by an expert panel of the National Institute of Allergy and Infectious Diseases, recommend that products with any allergen advisory statement be avoided by allergic individuals.
Q: What is the FDA doing to help prevent allergen cross-contact?
The FDA has made clear that the advisory statement is not to be used instead of current good manufacturing practices (CGMPs). These are FDA regulations that require adequate control of allergen cross-contact. In other words, manufacturers cannot just place an advisory statement on a product without first taking measures to prevent allergen cross-contact to the best degree possible. Under the Current Good Manufacturing Practice, Hazard Analysis, and Risk-Based Preventive Controls for Human Food rule, major food allergens are regarded as food hazards, and manufacturers are required to implement procedures, practices and processes when necessary to significantly minimize or prevent allergen cross-contact of major food allergens. This may include, but is not limited to, segregating allergens from non-allergens in the facility, scheduling products with allergens at the end of daily production cycles, where possible, and sanitation and cleaning of equipment after processing products containing allergens.
In addition, FDA inspections have allowed us to learn more about the various product challenges around preventing allergen cross-contact. With this information, we hope to provide more information to industry on how to prevent allergen cross-contact and, if this is not entirely possible, how to communicate the presence of potential allergen cross-contact to consumers.
Further, the FDA continues to develop methods to detect and determine how much of an allergen is present in various food products and to gain greater capacity to test for a variety of allergens. For example, the FDA developed the xMAP food allergen detection assay that can simultaneously detect 16 allergens, including sesame, in a single analysis, with a design that allows for expansion to target additional food allergens. These advances will enhance FDA’s ability to monitor the food supply for undeclared allergens and take action when they are found.
Q: How does the FDA respond if a product is found to have an undeclared allergen?
Every product found to have an undeclared allergen is reviewed on a case-by-case basis. A major food allergen is considered a serious potential hazard for the public. Thus, a product that is found to contain an undeclared major food allergen is likely to be subject to recall. In some cases, the FDA may determine that a product containing foods or food ingredients that are not major food allergens could also pose an allergen hazard to public health if they are not properly declared as ingredients on the product label and may recommend regulatory action accordingly.
Q: What do you think people should understand about the science of food allergies?
Although a lot of progress has been made, we still don’t have a cure for food allergies. We also don’t have all the diagnostic tools to identify individuals who are at increased risk for severe reactions or who will only have mild reactions. And, we don’t know which allergen dose exposures consistently lead to severe reactions. Without this knowledge, every individual with a food allergy is given the same advice that any allergen at any level needs to be avoided to prevent serious allergic reactions. The inherent difficulties of strictly avoiding any amount of or exposure to food allergen affects the quality of life of consumers and their families.
But there is hope on the horizon with particularly significant gains being made in the area of prevention and treatment of food allergies. Indeed, a landmark 2015 clinical study showed that early rather than later exposure to peanut in high-risk infants was associated with significantly reduced development of peanut allergies into childhood. This new evidence for peanut allergy prevention was corroborated by a National Institutes of Health expert panel and subsequently, in 2017, the FDA allowed a qualified health claim on the benefits of introducing peanuts to the diet of 4 to 10-month-old children at high risk of developing a peanut allergy. At the same time, new treatments for food allergies have been in the pipeline. In February 2020, FDA approved the first ever drug, Palforzia, for treatment of peanut allergy in children with the main goal of preventing severe allergic reactions that may occur with accidental exposure to peanuts. Advances in prevention and treatment are challenging public health norms that strict food allergen avoidance is required to prevent all adverse health consequences from food allergies. Now consuming some amount of food allergen and/or knowing actual amounts of or exposure to a food allergen in food is becoming ever more important in the management and prevention of food allergies.
Q: What are thresholds and how do they impact your work at the FDA?
A threshold can mean a lot of things to different people.
There can be an individual threshold for food allergens, which is the amount of an allergenic food protein a person has to consume before there is an adverse allergic reaction. Within the allergic population, individual thresholds may vary greatly. For example, some people allergic to peanuts may experience a reaction from a tiny amount, even a few milligrams of peanut, which is equivalent to grains of sand. Others may need to eat a gram or more, equivalent to whole peanuts. They are all allergic, but their individual thresholds are different.
There can also be a population threshold. This threshold can be derived from assessing a large number of individual patient thresholds and can be used to predict reaction risks within the food allergic population to certain levels or doses of allergen. Information from population threshold data has been used by some countries to establish reference limits for allergens that may or may not need to bear an allergen advisory statement to protect public health. This is an important area of study and FDA scientists are currently involved in international discussions conducted by the Codex Alimentarius and other authoritative bodies on this topic.
As of now, the FDA has not established thresholds for any major food allergen. However, this does not mean that we do not consider information related to allergen thresholds in our regulatory work. For example, the FDA may consider allergen threshold data in assessing the safety of ingredients exempted from FALCPA allergen labeling requirements. We continue to monitor and evaluate new science that has emerged in the past decade on population threshold dose response to a variety of food allergens.
Q: What can consumers do to protect their health?
First, consumers who think they have a food allergy should be tested and formally diagnosed by a health professional, and their allergic status should be regularly assessed over time. Studies have shown that as many as 3 in 4 people who think they have a food allergy may not have an allergy associated with life-threatening allergic reactions. Plus, a good number of food allergies are outgrown and/or may diminish over time. There is the potential that many individuals may be strictly avoiding food allergens without any true health reason or benefit. This not only reduces quality of life but may also place these individuals at risk for dietary deficiencies because they avoid nutritious foods.
Consumers who have received a formal diagnosis should be provided with all the tools and information to promptly and effectively manage allergic reactions should they occur. Also, in light of new treatments and threshold research aimed to provide more risk-based food allergen information, consumers should inquire about diagnostic testing, including food challenges, that can help provide better understanding of their individual thresholds or risks for reactions to certain allergen exposures.
Consumers should also inquire about possible treatments and/or clinical trials on the horizon. It’s worth exploring your options.
And finally, reading ingredient labels and advisory statements and avoiding products that list the allergen of concern on the label is a vital strategy for reducing the risk of allergic reactions. The FDA maintains updated information on its web pages and consumers can sign up for food recall alerts to learn when products with undeclared allergens are recalled from the market.
Q: “Information as power” around food allergens seems to be a motivating force for you. Can you share what else drew you to this area of science?
I’ve long been fascinated by the body’s immune system, and that continued through my medical school and training. A National Institutes of Health fellowship in allergy and immunology on cutting edge research was a very formative time for me. Food allergies were only beginning to become recognized at that time, but the field has since grown significantly and has a lot of opportunity for research and innovation. There are still old questions we haven’t yet answered, such as why food allergies develop, as well as new promises in emerging prevention and treatment strategies. This makes food allergy an exciting area to work in. Also, food is a big part of our culture and sense of community. My specific work is particularly gratifying, as it provides me opportunities to improve public and community health by assessing and communicating allergen risks so that the millions of consumers with food allergies can remain safe and reassured about the food products they are consuming. Knowing what the risks are and that these risks are being properly communicated is empowering.