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21/10/2013
1
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
*
*
*
*
*
*
*
*
*
*
*
*
*
*
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 [email protected]
VITAL Co-ordinatorGeorgina Christensen