# Presentation: 317908

## FDA Public Hearing on the Use of Advisory Labeling of Allergens in FoodsA Pediatric Allergist’s Perspective of the Food-Allergic Consumer’s Perspective  

**Scott H. Sicherer, MD**
**Jaffe Food Allergy Institute**
**Mount Sinai School of Medicine**
**New York, New York**

- September 16, 2008

## Disclosures

- Chair, American Academy of Pediatrics Section on Allergy
- NIH-NIAID Funding for studies
- Food Allergy Initiative Consultant and funding for studies
- Food Allergy & Anaphylaxis Network Advisor and funding for studies
- Author, Johns Hopkins University Press

**Notes:**
Scott H. Sicherer, M.D. is Associate Professor of Pediatrics at the Mount Sinai School of Medicine and a researcher in the Jaffe Food Allergy Institute at Mount Sinai.  Dr. Sicherer received his medical degree with honors from the Johns Hopkins University School of Medicine, and his pediatric training, including a Chief Residency, at Mount Sinai in New York City.  He completed a Fellowship in Allergy and Immunology at Johns Hopkins and then returned as Faculty to Mt. Sinai.   He is Board Certified in Pediatrics and in Allergy and Immunology and specializes in food allergies. His research interests, funded by the National Institutes of Health, Food Allergy Initiative and Food Allergy & Anaphylaxis Network include allergic diseases caused by specific foods such as peanuts, tree nuts, egg, seafood  and milk, the natural history of food allergy, atopic dermatitis, gastrointestinal manifestations of food allergies, epidemiology of food allergy, psychosocial issues associated with food allergies, modalities to educate physicians and parents about food allergy, and the genetics of food allergy.  He has published over 100 articles in scientific journals.  He has authored numerous book chapters in major pediatric and allergy textbooks.  He is a medical advisor to the Food Allergy & Anaphylaxis Network, the Food Allergy Initiative and others.  He is past-Chair of the Adverse Reactions to Foods Committee of the Academy of Allergy, Asthma and Immunology and current Chair of the Section on Allergy and Immunology of the American Academy of Pediatrics.  He is Associate Editor of the Journal of Allergy and Clinical Immunology.  He has authored three books for the lay audience regarding food allergies.  He has been consistently recognized as a “Top Doctor” by Castle-Connolly/New York Magazine.    

## Outline

**Prevalence/features of food allergy**
**Labeling issues**
**Consumer approach to advisory labels**
**Recent observations about advisory labels**
**Ongoing studies, clinical observations**
**Issues to consider**

**Notes:**
I will begin by taking this opportunity to review the scope and features of food allergy.  I will briefly review previous studies that revealed consumer problems with labeling prior to FALCPA and then review several studies we have done regarding advisory labels.   

## Prevalence Estimates

**Children under age 3: ~5-6%**
**Egg: 1.5%, Milk: 2.5%, Soy: 0.4%, Wheat:~0.4%**
**85% food allergies: egg, milk, wheat, soy, peanut, tree nut, seafood, (but any food possible, seeds emerging)**
**Adults: 3-4%**
**Shellfish (2%), Peanut (0.6%), Tree nuts (0.5%), fish (0.4%)**
**Less severe, fruits/vegetables (~5%)**
**Peanut allergy increasing (Sicherer 2003;Grundy 2003):**

**Notes:**
It has been estimated that ~12 million Americans have food allergies. There are limited data but a strong impression that food allergies, like other allergic conditions (asthma, hay fever, atopic dermatitis) have increased in the past decades.  
References:
Sicherer SH, Sampson HA. Food allergy. J Allergy Clin Immunol. 2006;117:S470-5.
Sicherer SH. Munoz-Furlong A, Sampson HA. Prevalence of Peanut and Tree Nut Allergy in the US determined by a Random Digit Dial Telephone Survey: A Five Year Follow-Up Study. J Allergy Clin Immunol. 2003;112:1203-7. 
Grundy J, Matthews S, Bateman B, Dean T, Arshad SH. Rising prevalence of allergy to peanut in children: Data from 2 sequential cohorts. J Allergy Clin Immunol 2002; 110(5):784-9.

## Prevalence Estimates (Cont)

**Severe/fatal: peanut, tree nuts, seafood (egg, milk)**
**One year morbidity (extrapolated from NEISS)**
**125,000 hospital ER visits**
**14,000 anaphylaxis**
**3100 Hospitalizations**

**Notes:**
The fatality rate of food allergy in the US has not been carefully documented.  The listed foods account form most of the fatalities reported from unregulated registries. The National Electronic Injury Surveillance System (NEISS) captures a nationally representative probability sample from hospital emergency departments (EDs) in the United States. In the paper cited, emergency department data from NEISS were analyzed to assess the magnitude and severity of adverse events attributable to food allergies. Emergency department events describing food-related allergic symptomatology were identified from 34 participating EDs from August 1 to September 30, 2003.  The data shown on the slide represents an extrapolation to 12 months based on presented 2 month data.

References:
Bock SA, Munoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol 2001; 107(1):191-3.
Bock SA, Muñoz-Furlong A, Sampson HA. Further fatalities caused by anaphylactic reactions to food, 2001-2006. J Allergy Clin Immunol 2007; 119(4):1016-8.
Ross MP, Ferguson M, Street D, Klontz K, Schroeder T, Luccioli S. Analysis of food-allergic and anaphylactic events in the National Electronic Injury Surveillance System. J Allergy Clin Immunol. 2008 Jan;121(1):166-71.

## Treatment=AVOIDANCE

**Education**
**Patient**
**Family/caregivers**
**School**
**Medications**
**Epinephrine**
**Antihistamines**
**Emergency access**
**911**
**Emergency room**

**Notes:**
Currently, the main therapy is to teach food-allergic consumers to avoid the trigger allergen. Accidental ingestion of the food can result in allergic reactions.  Anaphylaxis requires therapy with epinephrine (adrenaline). 
Reference:
Chapman JA, Bernstein IL, Lee, RE, Oppenheimer J, Nicklas RA, Portnoy, JM, Sicherer SH, Schuller DE, Spector SL, Khan D, Lang D, Simon RA, Tilles SA, Blessing-Moore J, Wallace D, Teuber SS. Food allergy: a practice parameter.  Ann Allergy Asthma Immunol. 2006 Mar;96(3 Suppl 2):S1-68.

## Food Allergen Labeling and Consumer Protection Act (Effective Jan 2006)

**What the law addresses:**
**Must disclose “major food allergens” in plain English words**
**Major food allergens: milk, egg, wheat, soy, peanut, tree nuts, fish, Crustacean shellfish**
**Must name specific tree nut, fish or shellfish (e.g. cashew, tuna, shrimp)**
**May list scientific name (e.g. casein) but if English word equivalent also used (e.g. milk)**

**Notes:**
Legislation requires that “major allergens” be listed on manufactured products either in the “Contains” list or as a parenthetical inclusion.  However, it is important to have patients read the label carefully each time they purchase products because ingredients may change. Specific nuts, fish, or shellfish must be listed and companies may continue to use scientific terms as long as the equivalent plain English word is listed.

## Manufacturing and Labeling Issues for Commercial ProductsBEFORE FALCPA 

- Altschul AS, Scherrer DL, Muñoz-Furlong A, Sicherer SH. Manufacturing and labeling issues for commercial products: Relevance to food allergy. _J Allergy Clin Immunol_ 2001;108:468.

**Notes:**
Prior to FALCPA regulations, several obstacles for the food-allergic consumer were identified. Study funded by FAAN.
Reference:
Altschul AS, Scherrer DL, Muñoz-Furlong A, Sicherer SH. Manufacturing and labeling issues for commercial products: Relevance to food allergy. J Allergy Clin Immunol 2001;108:468.

## Methods

**Analysis of unsolicited calls (1999-2000)**
**Food Allergy and Anaphylaxis Network (FAAN), a national, non-profit organization for families and individuals with food allergy**
**Categorization of calls**
**Type of complaint (e.g., allergic reaction, Good Samaritan notification of a problem)**
**Type of food involved**
**Type of labeling issue**
**Calls excluded**
**Lack of details, verification of a problem or repeat calls for the same product**

- 221 calls were analyzed

**Notes:**
The study was a convenience sample of calls to the Food Allergy & Anaphylaxis Network.

## Causal Foods

**Causal Foods**

- 32% of the calls were to report an allergic reaction
- Shown here are the trigger foods
- (Remaining calls were to report a problem)

**Notes:**
32% of the calls were in response to an allergic reaction.  The remainder included notification of observed problems. Shown here are the trigger foods.

## Slide 11

**Notes:**
This study predated FALCPA.  Also, advisory labels were not typically used.  The observations are in line with data from FDA studies described in the Federal Register.

## Interpretation of Commercial Food Ingredient Labelsby Parents of Food Allergic Children

- Joshi P, Mofidi S, Sicherer SH.  Interpretation of commercial food ingredient labels by parents of food allergic children.  _J Allergy Clin Immunol_ 2002;109:1019-21.

**Notes:**
Prior to FALCPA, we sought to determine accuracy of parental reading of food labels. Study funded by Mount Sinai.

Joshi P, Mofidi S, Sicherer SH.  Interpretation of commercial food ingredient labels by parents of food allergic children.  J Allergy Clin Immunol 2002;109:1019-21.

## Methods

**Survey of parents attending food allergy practice with child avoiding one or more:**
**egg, milk, wheat, soy, peanut**
**Booklet of actual labels 23 products**
**Milk-14, soy-7, peanut-5, egg-7, wheat-10**
**Parents indicate products containing the ingredients that they were avoiding **
- Would you need to avoid using this product, if yes, what food(s) does it contain that your child avoids?

**Notes:**
We undertook this study prior to FALCPA.  It may be useful to use this methodology in future testing of advisory labels.

## Subjects

**91 families**
**Foods avoided:**
**peanut-82****	****	****soy-27**
**milk-60****	****	****fish-55**
**egg-45****	****	****wheat-16**

## Results (Weighed for Number of Labels)

**Notes:**
These data are weighted for the number of labels containing each food. There were 14 labels containing milk, 7 containing soy, 5 containing peanut, 10 with wheat and 7 with egg.   We attributed the poor identification rates to problems such as scientific words (casein), poor label clarity (using symbols for dairy rather than words), having allergen ingredients amidst large numbers of ingredients.

## Post-FALCPA Survey (n=471)

- Ahn JACI 2008

**Notes:**

There is satisfaction with FALCPA but not about advisory labels.
Reference: Ahn SS, Furlong TJ, Weiss C, Sicherer SH. Consumer Attitudes and Response to New Food Allergen Labeling. (ABSTRACT) J Allergy Clin Immunol. 2008

## Food Allergen Labeling and Consumer Protection Act 

**What the law **_**does not**_** address:**
**Allergens not considered “major” (i.e. sesame or garlic) may not be identified**
**May be hidden using terms such as “spices” or “natural flavor”**
**Does not apply to non-crustacean shellfish (i.e. clam, squid)**
**“****May contain” advisory labeling is voluntary**

- *57% of FAAN conference attendees (n=410) did NOT know advisory labeling is currently voluntary (2008, unpublished)

**Notes:**
Our surveys of families indicate great satisfaction with the legislation except for several areas listed here.  Allergens that are not listed among the “major” allergens may not be disclosed, so patients may need to call manufacturers to determine certain ingredients when ambiguous terms (e.g., spices) are used for allergens that are not “major allergens.” This has been a big issue for seeds.  Consumers may not appreciate that advisory labeling is voluntary and not regulated.  
References:
Simons E, Weiss C, Furlong T, Sicherer SH. Impact of ingredient labeling practices on food-allergic consumers. Ann Allergy Asthma Immunol 2005; 95(5):426-8.

## Consumer Purchasing and Precautionary Labels

**P< 0.01 for each category 2006 vs 2003**

- Hefle JACI 2007

**Notes:**
To get a better understanding of food allergic consumers approaches to advisory labeling, we surveyed conference goers at Food Allergy & Anaphylaxis Network conferences in 2003 (625) and 2006 (645) in Chicago, Baltimore and NY.  Attendees are from all over the US.  Here are shown the rates of “would never purchase” for different labels.  Differences were significant indicating that the consumers are increasingly ignoring the advisory labels.
Study funded by FAAN and FARRP.
Hefle SL, Furlong TJ, Niemann L, Lemon-Mule H, Sicherer S, Taylor SL.  Consumer attitudes and risks associated with packaged foods having advisory labeling regarding the presence of peanuts. J Allergy Clin Immunol. 2007; 120(1):171-6.

## Results: Precautionary Labels

**83% of respondents reported that they had noticed new precautionary labels added to food products within the previous 12 month period**

**Notes:**
The survey did not ask why they would ignore a label advisory warning.  However,  we asked about their noticing a proliferation of labels and this was the case.   

## Provisional Label Themes:Consumer Response

**May contain...**
**May contain traces...**

**Manufactured in a facility that also processes...**
**Manufactured in a facility that also uses...**

**Manufactured on the same equipment...**
**Manufactured on shared equipment...**
**Manufactured on a line that processes...**

**Packaged in a facility that also packages...**

**~91% will not purchase**

**~85%**

**~70%**

**~65%**

- P = ns within category; p < 0.05 between categories

**Notes:**
Here we show that consumers differentially avoid the products based upon their interpretation of the label wording.  Consumers are assuming a degree of danger based upon the warning terms.

## Off the Shelf Tests

**2 lots per 179 items (7% positive)**
**Dose if serving eaten**

- Hefle et al JACI 2007

- 2/51

- 3/57

- 7/68

**Notes:**
But the amount of peanut found did not match the perceived risk!   A total of 179 different foods were purchased at retail outlets in Lincoln, Nebraska that had peanut allergy advisory labels.  Two different lot numbers from each product were obtained.  The products included nutrition bars, cereal bars, snack foods, frozen foods, desserts, instant meals, baking ingredients and bakery products.  The assay (Neogen Veratox quantitative Peanut Allergen Test)   has a lower limit of detection of 2.5 ppm (microgram/gram).  Peanut was detected in 13 products (one had a warning different from the categories on the chart).  The peanut was detected in 4/28 nutrition bars, 7/36 confections, 2/26 cereal/cereal bars.  Sine not all lots had the residue, the overall risk was 4.7%

## Proliferation of Advisory Labeling

- We undertook studies to determine the magnitude of use of advisory labels and additional concerns relevant to this issue for consumers

- 99 US stores, 49,604 products reviewed, 20,241 unique products, categorized into 24 food types.
- Overall, 17% of products had advisory labeling

- Data shown are preliminary-final analyses pending
- Chung JACI 2008 (abstract)
- Pieretti JACI 2008 (abstract)

**Notes:**
The data shown are preliminary and were reported in abstracts. Studies funded by Food Allergy Initiative

Chung D, Pieretti MM, Pacenza R, Slotkin T. Sicherer SH. Analysis of 1016 Commercial Food Ingredient Labels to review FALCPA compliance, use of advisory statements, and possible pitfalls for food allergic consumers (Abstract) J Allergy Clin Immunol 2008:121:S183
Pieretti MM, Pacenza R, Slotkin T, Sicherer SH. Frequency and Language Used in Allergen Advisory Labels: A survey of 20,241 commercially available products(Abstract).  J Allergy Clin Immunol 2008:121:S182

## Approximately 40% of advisory labeled products used “may contain” type terminology with the remainder nearly equally split as “shared equipment” and “within plant”

**Notes:**
The product categories with the highest rates of advisory labeling are shown here.  

- Examples:
- May contain
- May contain traces of
- Manufactured in a facility that also processes
- Manufactured on shared equipment with products containing
- Manufactured on a line that processes
- Packaged in a facility that also packages products containing
- Processed on equipment that makes products containing
- Produced in a plant which manufactures products containing
- Allergy information: produced in a facility that handles
- Made on equipment that also processes
- Allergen Information: Good manufacturing practices used to
-      segregate ingredients in a facility that also processes

- .

- Closer examination of a subset of products indicated numerous specific terms.
- Some products indicate GMP regarding allergens, some state they are “allergen-free” .
- Some mention they “may contain” allergens that are also listed as product ingredients.

**Notes:**
These are examples of various advisory label terms used

## Specific Allergens May Not Be Disclosed in Advisory Statements

- Tree Nut (80)

- Listed with Advisory Statement
- (not FALCPA regulated):

- 37%
- identified

- 63% not
- identified

## A Canadian Survey

- Survey of 583 families, Canadian children with peanut allergy
- 41.5% had reactions
- 33%: Complex, incomplete, mislabeling
- 32%-Failed to read
- 6%-ignored advisory

- Avoidance rates: 93% “not suitable for people with a peanut allergy”
- 87%: “may contain” “manufactured on same equipment”
- 72%:”May contain Traces”, “Packaged in..” “Facility that also processes”

- Purchase rates: 82%: “manufactured in a facility that is allergen free
- 		77%: “Product is allergen-free”

- Seth AA JACI 2007

**Notes:**
Seth AA, Waserman S, Kagan R et al. Improving Food Labeling for the Allergic Consumer. J Allergy Clin Immmunol (Abstract) 2007;121:S183

## Egg, Milk Peanut Contamination

- We have undertaken preliminary studies of allergens in advisory labeled products and ones that are similar but do not contain warnings.
- So far, we have seen ~5% of advisory-labeled products have allergen but “unlabeled” products have also been identified with contamination (<2%).

**Notes:**
This is a study in progress.  

## Questions I get

**Can I eat “May contain”?**
**Will eating trace amounts cause a problem?**
**A reaction?**
**Alter the course of the allergy?**
**Does “in a facility” mean less risk that “may contain”?**
**My child tolerated this product saying “may contain” so can he eat it now? **
**If there is no “advisory” did they forget or did they think about it and decide the product was safe?**

**Notes:**
These are common questions I hear from my patients.   Regulation of advisory labels should improve safety and reduce stress, confusion and improve quality of life.

## Thresholds

**The amount of food protein below which a reaction would not occur has not been fully established.**
**This “missing piece” of science complicates decisions about advisory labels.**

- Crevel RW, Ballmer-Weber BK, Holzhauser T, Hourihane JO, Knulst AC, Mackie AR, Timmermans F, Taylor SL. Thresholds for food allergens and their value to different stakeholders. Allergy. 2008 May;63(5):597-609.

**Notes:**
Not all allergic consumers react to trace amounts of a food allergen.  There are no simple tests to determine a level of allergen that a given person with a food allergy would tolerate and there are limited data regarding the implications of such exposures.  Some studies have tried to determine an amount of a food allergen below which no one has a reaction.  Such studies are difficult to undertake (selection of the most sensitive persons, performing feeding tests).  

Crevel RW, Ballmer-Weber BK, Holzhauser T, Hourihane JO, Knulst AC, Mackie AR, Timmermans F, Taylor SL. Thresholds for food allergens and their value to different stakeholders. Allergy. 2008 May;63(5):597-609.

## Conclusions-1

**A large number of Americans have food allergies and depend upon clear, accurate labeling**
**Label reading is not easy and is error- prone**
**FALCPA has generally improved safety and has satisfied consumers, However...**

## Conclusions-2

**Advisory labeling is proliferating**
**More products, more diversity of terms used, specific allergens not disclosed**
**Consumers “read in” risk based upon label terms, but the terms do not reflect risk**
**Consumers do not realize advisory labeling is voluntary (and unregulated)**