The presence of allergens in food is a serious public health safety concern that has prompted the U.S. Food and Drug Administration (FDA) to undertake a number of initiatives, two of which—on manufacturing and labeling—are described here. As background, each year the FDA receives reports of consumers who experience adverse reactions following exposure to allergenic substances in foods, and allergen-related national recalls of food products have increased steadily since 1990.[1]

Food allergies are abnormal responses of the immune system, especially the production of allergen-specific IgE antibodies, to naturally occurring proteins in certain foods that most people can eat safely FDA’s current allergen efforts are focused on the eight foods that most frequently cause serious allergic reactions in sensitive individuals and account for more than 90% of all food allergies: peanuts, soybeans, milk, eggs, fish, crustacea, tree nuts and wheat. Most consumers are aware of their specific sensitivities and rely on the food label to avoid foods that might result in an allergenic reaction. However, adverse reactions often occur when an allergen-sensitive consumer consumes an allergenic substance that has not been declared on the food label.

A recent report described a study in which FDA officials and state inspectors from Minnesota and Wisconsin conducted a joint study on peanut and egg allergens and cross-contact during manufacturing (“cross-contact” describes a situation in which traces of an allergen might end up in a product that does not normally contain the allergen). The study, conducted between September 1999 and March 2000, involved 85 small- to medium-sized bakery product, ice cream and candy manufacturing operations. If an investigator identified a labeling or cross- contact issue during an investigation, samples were collected for egg and peanut protein analysis. Eighteen of the 73 samples taken, or 25%, of the ice cream, bakery and candy food product samples tested positive for peanut allergens, although peanuts were not listed on the labels for these products.[2] Investigators found that companies unintentionally introduced food allergens into other foods through poor cleaning and production scheduling or improper cleaning of utensils. The inspectors also found that just over half of the manufacturers checked their products to ensure that the labels accurately reflected all of the ingredients.

Everyone—government, industry, and consumers—agrees that these findings illustrate a problem that needs fixing and a number of activities by the interested parties are in progress. FDA initiatives include publication of a compliance policy guide, the recent issuance of guidance material for investigators on how to conduct food allergen inspections, satellite training for federal and state regulatory personnel, and a public meeting on allergen labeling. The guidance, discussed in detail below, presents labeling and cross- contact issues that may occur during the manufacture of food products and result in undeclared allergens. The public meeting, also discussed here, explored allergen labeling issues.

MANUFACTURING: FDA ALLERGEN INSPECTION GUIDANCE
In August 2001, the agency announced the availability of guidance for investigators and other FDA personnel entitled “Guidance on Inspections of Firms Producing Food Products Susceptible to Contamination with Allergenic Ingredients.”[3] By familiarizing themselves with the guidance currently used by investigators, food manufacturers will have a clearer concept of the potential problems of which to be aware and how to address undeclared allergen issues.

Current regulations require that all added ingredients be declared on the label, yet there are a number of issues that have arisen in connection with undeclared allergens that are not clearly covered by label regulations. This guidance covers the following problem areas:

1. Products that contain one or more allergenic ingredients, but the label does not declare the ingredient in the ingredient statement;

2. Products that become contaminated with an allergenic ingredient due to the firm’s failure to exercise adequate control procedures, e.g., improper rework practices, allergen carry-over due to use of common equipment and production sequencing, inadequate cleaning;

3. Products that are contaminated with an allergenic ingredient due to the nature of the product or the process; e.g., use of common equipment in chocolate manufacturing where interim wet cleaning is not practical and only dry cleaning and product flushing is used;

4. A product containing a flavor ingredient that has an allergenic component, but the label of the product only declares the flavor, e.g., natural flavor. Under current regulations, firms are not required to declare the individual components of flavors, certain colors and spices. However, firms are encouraged to specifically label allergenic components/ingredients that are in spices, flavors and colors;

5. Products that contain a processing aid that have an allergenic component, but the label does not declare it. processing aids that contain allergenic ingredients are not exempt from ingredient declaration under the incidental additives regulation (21 CFR 101.100 (a)(3)), and thus, must be declared.    

The guidance that will be used by investigators to conduct allergen inspections covers the following areas:

Product Development. Determine if the firm identifies potential sources of allergens starting in the product development stage. For example, do they identify for each product all ingredients, ingredient components, processing aids, rework, processing steps, environmental conditions, and product carry-over due to use of common equipment? Are potential sources of allergen contamination identified at each step? Determine whether the products contain allergenic ingredients. For the most frequently produced products, request formulas. If formula information is refused, construct formulations by observing production.

Determine if the firm has assessed whether the packaging material used in direct contact with the product contains an allergen; e.g., foil coated with wheat ingredient as releasing agent. Does the firm use processing aids in the manufacture of the food? If so, do the processing aids contain allergenic ingredients? If so, what are the allergenic ingredients?

Does the firm use spices, flavors or colors that contain allergenic components? If so, do these spices, flavors or colors contain allergenic ingredients? If so, what are the allergenic ingredients?

Receiving. Determine whether the firm uses allergenic ingredients. Determine how these allergenic ingredients are handled at receiving and how they are identified and/or segregated in raw material storage. Determine if the firm stores any of these allergenic ingredients in bulk tanks. If yes, how are the contents of the bulk tanks identified? Determine what the firm’s procedure is for receiving ingredients into the bulk tank and what controls are in place to ensure proper product identity at all times. Determine if the firm receives any raw materials that are labeled with a statement, such as “this product was processed on machinery that was used to process products containing (allergen)” or “may contain (allergen)”. If so what ingredients? How are such statements reflected on the label of the firm’s finished product? Determine whether a label from each incoming lot of finished product labels is visually checked, either upon receipt or during production, to ensure the ingredient statement is correct for the intended product and that it is not a carton of mixed labels.

Equipment. Try to inspect the equipment before processing begins and document the adequacy of clean up. For example, is there a build-up of residual materials or pockets of residue in corners that may contain an allergen from previous runs? What is the condition of the conveyor belts? Is there any product build-up above processing zones? Also observe whether the firm checks the processing lines for cleanliness prior to production and whether they maintain a record of the check. Is this simply a visual check or does the firm use another method?

Determine whether the firm uses a Clean-In-Place (CIP) system for cleaning fixed lines, e.g. pipelines and tanks. If so, how do they ensure that the interior surfaces of the welds in the lines are smooth and will not entrap material during operation? Are the pipes free from dents? Determine if equipment is cleanable; e.g. stainless steel, accessible for cleaning. Determine if the firm has a written procedure for cleaning. Does the cleaning procedure include how to and at what frequency the equipment is cleaned? Describe the procedure. Determine if equipment and production lines are shared to process different products. Determine if any shared equipment is cleaned in between production of a product that contains allergens and one that does not; e.g. frill clean-up with detergent and water.

Processing. Determine what control measures, if any, are used by the firm to prevent the contamination of products that do not contain allergens? ‘What control measures does the firm employ? At what steps in production are the control measures instituted? Determine how the firm separates the production of those products that contain allergens from those that do not contain such ingredients. Is cross-contact likely to occur; e.g., airborne food particles, dust, allergen product residues from equipment, etc.? Determine if unpackaged, exposed product on the processing line is handled in a way that protects it against contamination. Determine if shared processing lines (equipment) are used. If yes, is allergen-containing product processed first or last?

Determine what is done with the portion of the product that is a mixture of the non-allergen product and allergen product; e.g., is it sent to waste or for animal feed or reworked? Determine whether the firm reworks product, and if they only rework like products. How is rework controlled? Is rework inventory reconciled at the end of the day? Determine how product to be reworked is stored and identified. Are rework containers clearly labeled? Determine how such rework holding vessels and containers are cleaned and stored.

Final Product Testing. Determine if the firm performs final product testing for the presence of allergens in products not intended to contain allergens. If so, for which allergens, and how is the testing documented? Determine what method of analysis is used and the sensitivity of that method. Determine if the testing is routine or periodic.

Investigators should use these questions solely for information gathering purposes. If the firm asks if FDA has methods for detecting allergens, the response should be that agency has not yet designated any method of allergen testing for regulatory purposes. There are, however, several commercial enzyme-linked immunosorbent assays (ELISA) kits for food allergens available in the marketplace. Currently, FDA is evaluating some of these kits and is also cooperating with kit manufacturers to conduct international collaborative studies to evaluate the performance of some of the ELISA-based methods.

Labeling. Determine if finished product label controls are employed; e.g., how are labels delivered to the filling and/or packaging area? Determine if product labels with similar appearances but different ingredients are controlled to ensure that the correct label is applied to the correct product. Determine if finished product packages are inspected prior to distribution to ensure that an allergen-containing product is labeled properly, or that labels are inspected during production. Is that inspection documented?

Determine if secondary ingredients are incorporated in the final product ingredient statement; e.g., the raw material mayonnaise, which contains eggs, oil and vinegar. Determine if the firm uses a statement such as “this product was processed on machinery that was used to process products containing (allergen)” or a statement such as “may contain (allergen)” if the firm uses shared equipment for products that contain and products that do not contain allergens. Any other such statement? Ask the firm why they believe they have to use the advisory statement. Determine if the finished product label reflects any advisory statements that were on the raw material labels; e.g., “this product was processed on machinery that was used to process products containing (allergen)”. Determine if the firm has a system to identify finished products made with rework containing allergenic ingredients. Does the final product label identify the allergens that may have been in the reworked product?

Any comments and suggestions regarding the guidance should be submitted to the Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Please refer to Docket No. 01D-0316.

THE CHALLENGE OF LABELING FOOD ALLERGENS: FDA PUBLIC MEETING
Held in Washington, DC, on August 13, 2001, the public meeting provided an opportunity for an information exchange. Specifically, the agency wanted to determine what additional actions might be warranted to further assist consumers with food allergies in identifying products containing food allergens and to support manufacturers in producing foods that are safe for consumers with food allergies by eliminating processing practices that result in the unintended addition of allergens to foods.

The agency requested written and oral comments in three topic areas relating to food allergens. The three focus areas were: (1) source or plain English labeling; (2) advisory labeling (e.g., “may contain” [name of allergen]); and (3) labeling of ingredients exempted from declaration (i.e., common or usual names of flavorings, spices and colors; incidental additives). A written transcript of the public meeting is available at www.fda.gov/ ohrms/dockets/dockets/oop_1322/00pl322tr.html. A complete overview of the queries posed by the agency for public comment has been published in the Federal Register.[4] The following is a summation of most of the published queries.

Source or Plain English Labeling. FDA recognizes that many of the common or usual names for ingredients listed in the ingredient statement are not understood by consumers to be derived from food allergens (e.g., “caseinate” or “whey” derived from “milk” and “albumin” derived from “egg”). The agency is considering whether additional labeling of food products is warranted in some instances to ensure that allergenic consumers are informed about the presence of food allergens.

Questions about source labeling include: What plain English terms would be understandable for the eight most common food allergens? What source or plain English labeling format or formats would be most informative to consumers? Are multiple formats confusing to consumers, and if so, is there a single format that would be preferable? If so, why? Should source or plain English labeling be voluntary or mandatory for the eight most common food allergens?

Advisory Labeling. Advisory labeling includes statements on food packaging labels such as “may contain peanuts” or “made on shared equipment.” FDA’s current position is that advisory labeling should not be used in lieu of adherence to Good Manufacturing Practices (GMPs) because adhering to GMPs is essential for effective reduction of adverse reactions. Food that contains an undeclared allergen due to cross-contact or other sources may he considered adulterated under section 402(a)(4) of the Federal Food Drug and Cosmetic Act (the act) (21 U.S.C. 342(a)(4)), because it has been prepared, packed or held under insanitary conditions that may render the food injurious to health. Thus, FDA believes advisory labeling should not be the norm, and manufacturers should strive to eliminate the presence of allergenic materials that are not intentionally added to a specific food product.

However, FDA recognizes that advisory labeling is an attempt by manufacturers to inform consumers of the possibility that cross-contact may have occurred such that the product contains an allergenic substance. FDA is considering whether, and if so, under what circumstances advisory labeling should be permitted when appropriate manufacturing controls are not sufficient to guarantee the absence of allergenic substances in a particular food product.

The agency asks the following questions: Under what circumstances, if any, should advisory labeling statements be permitted, and what impact would those circumstances have on manufacturers and on consumers? Are there better alternatives for advisory labeling than the type of wording that currently exists (e.g., “May contain [name of specific allergen],” “Made on shared equipment,” “Manufactured in a facility that also processes [name of specific allergen]”)? Do such statements adequately inform consumers of possible cross-contact with allergenic materials? How do consumers interpret the wording of such labeling? Should advisory labeling statements be prescriptive (i.e., one or more specific statements) or flexible? And finally, where should advisory labeling statements be located on the food label? How prominent should advisory labeling statements be on the label? Should the location and prominence of advisory labeling statements be prescribed?

Labeling of Ingredients Exempted From Declaration. The collective naming of flavors, spices, and certain colors is one of the exemptions to the requirement for the complete labeling of ingredients (section 403(i) of the act). This exemption permits these ingredients to be listed collectively in the ingredient statement without naming each by its common or usual name. Food labels with collectively named flavorings, spices, and colors may not adequately inform individuals who wish to avoid allergenic substances, particularly when the allergenic substance is not specifically identified.

FDA believes that the declaration of allergenic ingredients in individual flavorings, spices, and colors is necessary for consumers to adequately protect themselves from exposure to food allergens. On a case-by-case basis, FDA has used notice-and-comment rulemaking to require the declaration of individual allergenic flavorings, spices, and colors, and is now considering whether continuing to address allergenic flavorings, spices and colors on a case-by-case basis is the best approach available to the agency.

Questions for public comment relate to the alternatives available to the agency and include, for example: Should the agency continue to address the labeling of individual allergenic flavorings, spices, and colors on a case-by-case basis, or should there be a generally applicable policy? Should the information on allergenic components of flavorings, spices, and colors be included in the ingredient list? Is there a better location or format for this information? Explain. For individual flavorings, spices, or colors that contain one of the eight most common allergens, should listing the common or usual name of the individual flavoring, spice, or color on the product labeling be voluntary or mandatory?

The labeling of incidental additives is also being discussed. Incidental additives include substances that are present in a food at insignificant levels and have no technical or functional effect in the finished product, such as, processing aids and substances that may migrate to the food from equipment or packaging. FDA has stated that because very small amounts of some allergenic substances can cause serious allergic responses, allergens that cause serious allergic reactions cannot be considered to be present at an “insignificant” level in the food. The agency has stated that all allergenic substances introduced as ingredients or as the result of manufacturing processes do not qualify as incidental additives and must be declared in the ingredient statement on the label of a food product.

Questions about this relate to gathering information and exploring educational alternatives to increase manufacturer understanding. What, if any, minor ingredients would manufacturers be unlikely to recognize as containing food allergens and therefore not include on the label, and what kinds of manufacturing processes would manufacturers be unlikely to recognize as unintentionally introducing food allergens? When products that contain food allergens will be further processed or repacked, is food allergen labeling sufficient on such intermediate products or is it necessary to have clearer labeling on intermediate products to ensure that food allergens are appropriately declared on the retail packaging of the final product? Should the agency codify its policy to specifically state that incidental additives that are food allergens are not exempt from labeling and must be declared in the ingredient statement on the label?

REMINDER
The agency is encouraging food manufacturers and other interested parties to submit detailed responses to these questions by Oct. 29, 2001. You may do so by mail (Attn: Dockets Management Branch (HFA-305), FDA, 5630 Fishers Lane, Room 1061, Rockville, MD 20852); by e-mail (FDAdockets@oc.fda.gov). Please refer to Docket No. 00P-1322.

Kathy L. Gombas is the deputy director of the Division of HACCP Programs, CFSAN, FDA. Her division provides technical expertise and leadership in areas of food safety programs and HACCP to support the development of agency policies, regulations, standards and training.

Ellen M. Anderson, Ph.D., is a chemist in the Division of Standards and Labeling Regulations, CFSAN, FDA. Her division provides guidance and establishes policies for regulating food standards and product label statements on foods and dietary supplements.

REFERENCES
1. Falci, Kenneth, Kathy Gombas and Elisa Elliot. Allergens: An FDA priority. Food Safety Magazine, (7)2. February/March 2001.
2. Formanek Jr., Raymond. Food allergies: When food becomes the enemy. FDA Consumer. July/August 2001.
3. Federal Register. 66 FR 42869. August, 15, 2001. (www.fda.gov/phrms/dockets/98fr/08150lc.pdf).
4. Federal Register. 66 FR 38591. July 25, 2001. (www.cfsan.fda.gov/~lrd/fr010725.html).

Common Symptoms of an Allergic Reaction to Food

Only about 1.5% of adults and up to 6% of children younger than three years old in the U.S.—about 4 million people—have a true food allergy, according to researchers who have examined the prevalence of food allergies.

It’s critical for people who have food allergies to identify them and to avoid foods that cause allergic reactions. Some foods can cause severe illness and, in some cases, a life-threatening allergic reaction (anaphylaxis) that can constrict airways in the lungs, severely lower blood pressure, and cause suffocation by the swelling of the tongue or throat.

An estimated 150 Americans die each year from severe allergic reactions to food, says Hugh A. Sampson, M.D., director of the Elliot and Roslyn Jaffe Food Allergy Institute at Mount Sinai School of Medicine in New York City and a food allergy expert. Symptoms typically appear within minutes to two hours after a person has eaten the food to which he or she is allergic: tingling sensations in the mouth; swelling of the tongue and throat; difficulty breathing; hives; vomiting; abdominal cramps; diarrhea; drop in blood pressure; loss of consciousness; and death.

—Source: FDA Consumer, August 2001