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Managing Allergens in Food

Simon Brooke-Taylor PhD27 September 2013

Adverse Reactions to Food

Immune responses to food

▪ IgE mediated - food allergy – usually protein

▪ non-IgE (eg coeliac disease - gluten)

Food Intolerance

▪ chemical or physiological reaction to food (eg lactose)

Toxicity

• Foodborne pathogen

• Pharmacologically active food component

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IgE Mediated Food Allergy

Utrecht Center For Food Allergyhttp://ucfa.nl/food-allergy/mechanisms/

Symptoms of Food Allergy

• Itching, burning and swelling around the mouth

• Runny nose

• Skin rash (eczema)

• Hives (urticaria – skin becomes red and raised)

• Diarrhoea, abdominal cramps

• Breathing difficulties, including wheezing and asthma

• Vomiting, nausea

• Anaphylaxis - Can be Fatal

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Prevalence of Food Allergy

• 4% of all Americans (approximately 12 million)

• 3.7% of adults

• 6% of children under 3 years of age

• Most food allergies resolve in first 10 years of life

• Cow milk allergy in 2.5%

• Egg allergy in 1.3%

• Peanut allergy in 0.8

• peanut, tree nut, fish, and shellfish allergies often

lifelong

• eg only twenty percent outgrowing peanut allergy

Peanut

• N Europe, N America, Australia, New Zealand

• why not Asia?

• preparation, boiled/fried vs roasted?

Celery

• Switzerland

Chestnut

• Korea

Food Allergy - Regional Variation

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How Allergens Get Into Food

Direct Addition

• Allergens + Products of Allergens

• Food Ingredients

• Food Additives

• Processing Aids

Cross-Contact

• Transport & storage of raw materials

• shared equipment/facilities

• Common processing facilities

Establishing Food Allergen Thresholds

Why?

• Mandatory labelling exemptions

• Precautionary labelling

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Mandatory Allergen Labelling

Cereals containing gluten

Milk

Egg

Crustacea

Molluscs(EU)

Fish

Peanuts

Soybeans

Sesame seeds

Tree Nuts (EU named nuts)

Added Sulphites ≥10 mg/kg

Celery (EU)

Lupins (EU)

Mustard (EU)

Exemptions case by case

isinglass ANZ, EU

fish gluten(EU)

coconut (ANZ)

alcohols from cereals (ANZ,EU),

whey (EU), treenuts (EU),

glucose syrups and maltodextrin

(EU)

lactitol (EU)

refined soybean oils, tocopherols,

phytosterols and stanols (EU)

Tree Nuts of Concern

• almonds

• Brazil nuts

• cashews

• hazelnuts (filberts)

• macadamia nuts

• pecans

• pine nuts (pignolias)

• pistachio nut

• walnuts.

Peanuts are part of the legume family (like soy) and are not tree

nuts

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Precautionary Labelling

2005 – Concern about overuse of “may contain”

AFGC Allergen Risk Assessment Project

Development of a standardised allergen risk

assessment tool which can be used to assist in

determining appropriate voluntary allergen labelling

statements

VITAL

Voluntary

Incidental

Trace

Allergen

Labelling

System

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•PIF•VITAL Guidelines•VITAL Calculator•Unexpected Allergens in Food•links of international allergen regulations•Presentations•Helpline

download from website (free)

Alllergen Bureau Resources

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•Guidance Document – more detailed •New definitions and expanded explanations •Attempts to avoid common mistakes •Includes detailed information about allergen analysis•Available at www.allergenbureau.net

VITAL 2.0 Procedure

Elements of VITAL

Incorporate in HACCP Food Safety Programme

1. Ingredient and Processing Impact Assessment

2. Compare with VITAL Grid – integrated in VITAL calculator

3. Identify Action Levels & recommended labelling– may be present: allergen

4. Record Assumptions, Validate, Monitor

labelling is not an excuse for not implementing GMP!

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Ingredient and Processing Impact Assessment

• Identify• relevant allergens (intended country of sale)

• added allergens

• Identify and quantify cross contact allergens • due to ingredients

• due to processing

• VITAL Calculator• Calculate total cross contact allergen in final product

• Identify typical portion / serving size

• Compare with threshold concentration from VITAL Grid

• if ACTION Level 2• Can procedures be modified to reduce cross-contact?

• review before deciding to label

VITALCALCULATOR

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VITALGRID

Embedded in

VITAL calculator

VITAL Grid & Action Levels

Reference Dose

mg allergen protein

Reference Amount

or

Serving Size

gm of food

Action Level 2

precautionary label

Action Level 1

no label

+Action Level Threshold

mg/kg

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VITAL Grid v2.2

Reference Quantity 100 gm

Allergen Reference

Dose

Total protein

(mg)

Level of protection ActionNo

Level 1Label

ActionPrecautionery

Level 2label

Peanut 0.2 ED01 <2 ppm >2 ppm

Milk 0.1 ED01 <1 ppm >1 ppm

Egg 0.03 ED01 and 95% lower

confidence interval of the ED05

<0.3 ppm >0.3 ppm

Tree Nuts 0.1 ED01 and 95% lower

confidence interval of the ED05

<1 ppm >1 ppm

Soy 1 95% lower confidence interval

of the ED05 for soy flour

<10 ppm >10 ppm

Gluten

containing

cereals

1 95% lower confidence interval

of the ED05

<10 ppm <10 ppm

Sesame 0.2 95% lower confidence interval

of the ED05

<2 ppm >2 ppm

Crustacea 10 95% lower confidence interval

of the ED05

<100 ppm >100 ppm

Fin fish 0.1 LOEL <1 ppm >1 ppm

Mustard 0.05 95% lower confidence interval

of the ED05

<0.5 ppm >0.5 ppm

Lupin 4 95% lower confidence interval

of the ED05

<40 ppm >40 ppm

Risk Based Thresholds for VITAL

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Allergen Cross Contact - Population at Risk

from Crevel et al 2008

Original VITAL Scientific Approach

• Key data source FDA Threshold Working Group Report (2006)

• Used LOAELs from FDA TWG tables

• Applied uncertainty factors (UF) to set reference doses

• Expressed action levels in concentration (ppm) rather than amount of protein(mg);

• 5 g serving size (teaspoon/mouthful)

• Most VITAL min levels set at >2 ppm (exceptions fish, milk, soy, gluten)

• very conservative

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Vital Review 2010

Quantitative risk assessment

• Some allergic individuals are more sensitve than

others!

• Bindslev-Jensen et al (2002) possible to derive a

statistically based populaton dose response curve

for allergen reactions

• Crevel et al (2007) - concept of eliciting dose (ED)

representative of the whole allergic population

• EDp - dose of allergen that produces a response in p% of

the allergic population.

Dose Distribution Modelling

from Crevel et al Food Chem Toxicol 2007

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100%

50%

5%10%

log normal,

log logistic, or

Weibull model

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Dose Distribution Modelling

Vital Review 2010

Quantitative risk assessment

• Bindslev-Jensen et al (2002) possible to derive a

statistically based dose response curve for allergen

reactions

• Crevel et al (2007) - concept of eliciting dose (ED)

representative of the whole allergic population

• EDp - dose of allergen that produces a response in p% of

the allergic population.

• But how to access data for quantitative modelling?

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VITAL Scientific Expert Panel (VSEP) 2011

• Role: Advise Allergen Bureau on VITAL review

• Collaboration between:

• The Allergen Bureau;

• FARRP (Food Allergy Research and Resource Program (University of Nebraska) and;

• TNO (The Netherlands Organisation for Applied Scientific Research)

• Access to new data sources

• Expertise in Allergen Risk Assessment

VITAL Scientific Expert Panel (VSEP)

Panel Members:• Dr Steve Taylor (FARRP)• Dr Joseph Baumert (FARRP) ,

• supported by Mr Benjamin Remington (FARRP),• Dr Geert Houben (Program Manager Food Safety,TNO. NL)• Dr Rene Crevel (Allergy & Immunology, Unilever)• Dr Katie Allen (Paediatric Gastroenterologist/Allergist , Royal Chrildrens

Hospital, University of Melbourne), • supported by Ms Jennifer Koplin

• Dr Simon Brooke Taylor (Food Safety & Risk Analysis Consultant, AB)

• The VSEP received significant support from Astrid Kruizinga, Ellen Dutman & Harrie Buist (TNO)

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VSEP principles

• Scientifically & clinically sound, defensible and transparent

• Reference Dose expressed as mg of total protein with Action Level determined using the reference amount or serving size

• Exquisitely allergic consumers not accounted in VITAL

• Assume do not eat processed foods without seeking advice from manufacturer first

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VSEP principles (cont)

• Level of Acceptable Risk

• protection for vast majority of allergic individuals 95-99%

• Reference doses set with highest degree of safety

• Increasing availability of clinical data = increasing confidence in models

• Drives research to fill the data gaps

• Potentially opens up choice to a larger number of ‘safe’ foods

• Reference Doses subject to ongoing review

The VSEP Overarching Scientific Approach

Quantitative risk assessment

• Threshold predictive for the whole population• Representative population weighted to include both individuals who react

to very low amts & those who require large amts to provoke response

• Statistically based risk assessment - population thresholds• Requires individual threshold doses from a sufficiently large number of

allergic individuals

• Analysis of the clinical literature conducted

• determine if sufficient quantity and quality of published and unpublished data accessible

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Working Examples

Probability distribution models for individual peanut thresholds (as whole peanut). Published data..

(a) Log-Logistic, (b) Log-Normal, (c) Weibull. Taylor et al 2009

ED10 doses for whole peanut as assessed by three probability distribution models.

Distribution ED10 95% CILog-Normal 8.4 4.1, 17.4Log-Logistic 8.1 3.6, 18.4Weibull 6.3 2.3, 17.0

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•Probability distribution curves (Weibull) of thresholds for peanut, hazelnut, cashew nut, cow’s milk and hen’s egg (as discrete doses in milligram of total protein of the allergenic food) in an allergic pediatric population. Distribution based on LOAEL and NOAELs for objective symptoms.

from Blom et al 2013

VSEP data point summary by Allergen

Allen et al 2013

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VSEP Recommended Reference Doses

Allergen Protein Level (mg) VITAL implementation

Peanut 0.2

Milk 0.1

Egg 0.03

Hazelnut 0.1 Used as generic tree nut value

Soy 1.0 Soy protein isolates not soy milk

Wheat 1.0 Coeliac & wheat allergic population

Cashew 2.0

Mustard 0.05

Lupin 4.0

Sesame 0.2

Shrimp 10.0

Celery NA

Fish NA original VITAL value applied

Overview

• VSEP approach used all available existing published data plus some unpublished data

• Implemented in VITAL 2 in 2012• ppm determined on actual serving size

• VITAL grid levels protect 95-99% of allergic consumers • 99% desirable when sufficient data exists to allow statistically sound estimates

• Risk of mild, transitory objective reactions typically requiring no pharmacological intervention

• Exquisitely sensitive allergic consumers may not be fully protected (assume do not consume packaged foods)

• No additional uncertainty factors needed because of use of ED01 or lower 95% confidence interval of ED05

• Allergic populations in trials appear to be representative or skewed toward more highly sensitive (referral clinics, immunotherapy studies)

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VITAL Grid v2.2

Reference Quantity 100 gm

Allergen Reference

Dose

Total protein

(mg)

Level of protection ActionNo

Level 1Label

ActionPrecautionery

Level 2label

Peanut 0.2 ED01 <2 ppm >2 ppm

Milk 0.1 ED01 <1 ppm >1 ppm

Egg 0.03 ED01 and 95% lower

confidence interval of the ED05

<0.3 ppm >0.3 ppm

Tree Nuts 0.1 ED01 and 95% lower

confidence interval of the ED05

<1 ppm >1 ppm

Soy 1 95% lower confidence interval

of the ED05 for soy flour

<10 ppm >10 ppm

Gluten

containing

cereals

1 95% lower confidence interval

of the ED05

<10 ppm <10 ppm

Sesame 0.2 95% lower confidence interval

of the ED05

<2 ppm >2 ppm

Crustacea 10 95% lower confidence interval

of the ED05

<100 ppm >100 ppm

Fin fish 0.1 LOEL <1 ppm >1 ppm

Mustard 0.05 95% lower confidence interval

of the ED05

<0.5 ppm >0.5 ppm

Lupin 4 95% lower confidence interval

of the ED05

<40 ppm >40 ppm

Thank you

Allergen Bureau VITAL Mgt TeamRobin Sherlock - DTS FACTa

Fiona Fleming - FJ Fleming Food ConsultingKirsten Grinter – Nestle Australia

Allergen Bureau Scientific Risk Analysis ConsultantSimon Brooke Taylor

Allergen Bureau Mangementmanagement@allergenbureau.net

VITAL Co-ordinatorGeorgina Christensen

vital@allergenbureau.net

Informationinfo@allergenbureau.net