Managing Allergens in Food Simon Brooke-Taylor PhD 27 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 1
IgE Mediated Food Allergy Utrecht Center For Food Allergy http://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 2
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 Food Allergy - Regional Variation Peanut N Europe, N America, Australia, New Zealand why not Asia? preparation, boiled/fried vs roasted? Celery Switzerland Chestnut Korea 3
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 4
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 5
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 Voluntary Incidental Trace VITAL Allergen Labelling System 6
Alllergen Bureau Resources PIF VITAL Guidelines VITAL Calculator Unexpected Allergens in Food links of international allergen regulations Presentations Helpline download from website (free) 7
VITAL 2.0 Procedure 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 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! 8
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 VITAL CALCULATOR 9
VITAL GRID Embedded in VITAL calculator VITAL Grid & Action Levels Reference Dose mg allergen protein Action Level 2 precautionary label Action Level Threshold + mg/kg Reference Amount or Serving Size gm of food Action Level 1 no label 10
VITAL Grid v2.2 Reference Quantity 100 gm Allergen Reference Dose Total protein (mg) Level of protection Action Level 1 No Label Action Level 2 Precautionery label Peanut 0.2 ED01 <2 ppm >2 ppm Milk 0.1 ED01 <1 ppm >1 ppm Egg 0.03 ED01 and 95% lower <0.3 ppm >0.3 ppm confidence interval of the ED05 Tree Nuts 0.1 ED01 and 95% lower confidence interval of the ED05 Soy 1 95% lower confidence interval of the ED05 for soy flour Gluten containing cereals 1 95% lower confidence interval of the ED05 Sesame 0.2 95% lower confidence interval of the ED05 Crustacea 10 95% lower confidence interval of the ED05 <1 ppm >1 ppm <10 ppm >10 ppm <10 ppm <10 ppm <2 ppm >2 ppm <100 ppm >100 ppm Fin fish 0.1 LOEL <1 ppm >1 ppm Mustard 0.05 95% lower confidence interval of the ED05 Lupin 4 95% lower confidence interval of the ED05 <0.5 ppm >0.5 ppm <40 ppm >40 ppm Risk Based Thresholds for VITAL 11
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 12
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 13
Dose Distribution Modelling 100% 50% log normal, log logistic, or Weibull model 10% 5% 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? 14
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) 15
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 16
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 17
Working Examples Probability distribution models for individual peanut thresholds (as whole peanut). Published data.. ED10 doses for whole peanut as assessed by three probability distribution models. Distribution ED10 95% CI Log-Normal 8.4 4.1, 17.4 Log-Logistic 8.1 3.6, 18.4 Weibull 6.3 2.3, 17.0 (a) Log-Logistic, (b) Log-Normal, (c) Weibull. Taylor et al 2009 18
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 19
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) 20
VITAL Grid v2.2 Reference Quantity 100 gm Allergen Reference Dose Total protein (mg) Level of protection Action Level 1 No Label Action Level 2 Precautionery label Peanut 0.2 ED01 <2 ppm >2 ppm Milk 0.1 ED01 <1 ppm >1 ppm Egg 0.03 ED01 and 95% lower <0.3 ppm >0.3 ppm confidence interval of the ED05 Tree Nuts 0.1 ED01 and 95% lower confidence interval of the ED05 Soy 1 95% lower confidence interval of the ED05 for soy flour Gluten containing cereals 1 95% lower confidence interval of the ED05 Sesame 0.2 95% lower confidence interval of the ED05 Crustacea 10 95% lower confidence interval of the ED05 <1 ppm >1 ppm <10 ppm >10 ppm <10 ppm <10 ppm <2 ppm >2 ppm <100 ppm >100 ppm Fin fish 0.1 LOEL <1 ppm >1 ppm Mustard 0.05 95% lower confidence interval of the ED05 Lupin 4 95% lower confidence interval of the ED05 <0.5 ppm >0.5 ppm <40 ppm >40 ppm Thank you Allergen Bureau VITAL Mgt Team Robin Sherlock - DTS FACTa Fiona Fleming - FJ Fleming Food Consulting Kirsten Grinter Nestle Australia Allergen Bureau Scientific Risk Analysis Consultant Simon Brooke Taylor Allergen Bureau Mangement management@allergenbureau.net VITAL Co-ordinator Georgina Christensen vital@allergenbureau.net Information info@allergenbureau.net 21