Translating allergen management limits into practice René Crevel ILSI Food Allergy Task Force VIII Updates on Food Safety Symposium Sao Paulo, Brazil November 10, 2016
Outline Limits for allergens: current status and issues Limits for allergens Why are they needed? What are they meant to achieve? How can we effectively use limits? Application to precautionary allergen labelling Current developments in Europe
Limits for allergens: current status and issues
Risk management: translating the risk assessment to protection of public health Feasibility within regulatory and operational constraints Avoiding unintended consequences Need to balance potentially conflicting requirements Potential effect on other safety parameters Potential effect on environment Waste Adequate protection and over-use of PAL Quality of life for allergic individuals 4
Current approach to limits for allergens: the safety issue Food production involves: the deliberate use of allergens as ingredients the unintended presence of allergens in products, despite all measures to avoid them. Legal and regulatory response to the issue: Hazard-based for ingredients: if it s there, it must be labelled Varied and often poorly-defined for unintentionally present allergen These account for the most salient safety issues
Current approach to limits for allergens: the consequences Lack of harmonised approaches to assessing, managing and communicating risk, leading to: Diverse standards dependent on FBO s knowledge and understanding, and risk perception, lacking transparency No agreed single, consistent level of safety for each allergen across food products Inconsistent standards for application of PAL Consumer confusion and lack of trust over safety of products Loss of credibility of PAL Increased risk to allergic consumers
Limits for allergens Why are they needed? What are they meant to achieve?
Limits for allergens: what do we need them for? Primary purpose of limits for allergens is to protect allergic consumers effectively by minimising the incidence of reactions This will also protect food business operators (FBOs) if well-implemented Limits will do this by Providing a single, consistent benchmark for allergen management decisions by FBOs relating to unintentional allergen presence, including application of PAL Fostering good practice in assessing the risk from unintended allergen presence Ensuring that PAL s value is restored and maintained, so that it is an effective tool
Unintended allergen presence (UAP) The allergen is not an ingredient The presence can occur at any point in the food supply chain, e.g.: In the fields: commingling with previous crop During transportation: crosscontact in bulk containers etc During storage at the manufacturing location(s) During manufacture, including packaging Deliberate presence (Ingredients) Ingredient labelling Formulation, traceability Two scenarios Unintended presence (cross-contact, etc) Allergen risk management Risk assessment Integrated Allergen Management programme 9
Unintended allergen presence (UAP) Presence varies according to: the production process, the source of unintended presence the physical form of the allergen (readily dispersible or particulate) The quantity present varies and could be: a very low level of allergen present in all units of the product in a proportion of units only allergen in particulate form, most units may not have any allergen, but where it occurs, it may be sufficient to provoke a severe reaction, so resulting in a rare event, but with serious consequences 10
What does/can a PAL statement mean? Dunngalvin A, Chan CH, Crevel R et al. Precautionary Allergen Labelling: Perspectives from key stakeholder groups. Allergy 2015, 70, 1039-1051 11
Current situation: allergen management and PAL Industry is uncertain about how much to do in managing allergens and when to use or not to use PAL Industry cannot therefore communicate effectively to allergic consumers and other stakeholders about management of unintended allergen presence PAL is failing as a risk management tool, because it has lost its credibility amongst the target population. The reason for this loss in credibility, is a proliferation of injudicious labelling practices across industry.
PAL is not meeting its objectives Allergic consumers are disregarding PAL statements to a significant extent 90% Ben-Shoshan et al. JACI (2012) 129: 1401 80% 70% 60% 50% 40% 30% 20% 10% 0% 40% Cochrane et al. Clin Trans Allergy (2013) 3: 31. 35% 30% 25% 20% 15% 10% 5% 0% Never purchase if labelled 13
What is the problem with Precautionary Allergen Labelling (PAL)? Ingredients: 2 Annex II foods PAL: 9 Annex II foods Ingredients: 1 Annex II food PAL: 10 Annex II foods PAL statement not expected on product 14
Current situation These practices in turn are driven by: confusing terminology giving the impression of a risk hierarchy, unsupported by experimental evidence lack of transparency over its use faulty beliefs among consumers concerning the framework in which it is used (e.g. that it is mandatory) inappropriate use, e.g. on products where it is unexpected lack of agreed standards for application (no harmonized risk assessment)
When PAL leads to the wrong risk conclusions Allergic reaction to peanut residue kills 22-year-old Twin Cities man Some of the facts. He was diligent about avoidance of peanuts Days before, he had eaten candy from the same container with no reaction Had experienced a few reactions over the years but recovered without going to hospital However with so many foods containing nut warning labels, had found he could eat many labelled foods without a reaction Had eaten chocolates from the same box on the previous days (Friday and Saturday) Ate 3 or 4 chocolates on Monday Was fine when he left his mother s house 1-2 hours later In the 20 minutes he took to reach his father s house, started to react Was unconscious within a few minutes of arriving http://www.startribune.com/peanut-allergy-kills-22-year-old-twin-cities-man/366152021/
How can we effectively use limits? Application to precautionary allergen labelling (PAL)
Food Allergens: dose and effect
Why is it so difficult to define thresholds for PAL? 100 100 75 Risk Profile Proportion of products affected (%) 50 75 Observance of precautionary labelling (%) 25 50 0 0.1 1 10 100 Reference dose..we believe that we should set a gluten threshold level for gluten free labeling that best assists most individuals with celiac disease in adhering life-long to a gluten-free diet without causing adverse health consequences...moving to a definition of gluten-free that adopts a criterion that is much lower than < 20 ppm gluten could have an adverse impact on the health of Americans with celiac disease.(us FDA) 19
VITAL 2.0 Reference doses Allergen Basis of Reference Dose VITAL 2.0 Reference dose (mg protein/serving) Level of protection of RD Peanut ED01 0.20 99 4.00 Milk ED01 0.10 99 2.00 Egg ED01 0.03 99 0.60 Hazelnut* ED01 0.10 99 2.00 Soy 95%LCI ED05 1.00 >95 20.00 Concentration in a 50g serving ( Action level ) (mg/kg) Wheat 95%LCI ED05 1.00 >95 20.00 Mustard 95%LCI ED05 0.05 >95 1.00 Lupin 95%LCI ED05 4.00 >95 80.00 Sesame 95%LCI ED05 0.20 >95 4.00 Shrimp 95%LCI ED05 10.00 >95 200.00 Celery Insufficient data Fish Insufficient data
What do these reference doses mean? 8 37 mg of peanut protein (32 148 mg of whole peanut) 21
What do these reference doses mean? (continued) 24 patients Dose escalation: 0.5mg to 2286mg peanut protein Only small percentage of mild reactions up to 0.4mg peanut protein 6662 doses delivered, 1023 symptoms recorded, 3% severe, no severe symptoms below 25mg peanut protein 22
What do these reference values mean? The clinical data (1) Anaphylaxis developed at a cumulative dose of peanut of 0.02g to 11.7g (i.e. from 5mg to 2750mg of peanut protein) VITAL 2.0 Reference dose for peanut is at least 25-fold lower than the lowest dose to provoke an anaphylactic reaction 23
What do these reference doses mean? The clinical data (2) 869 children challenged Starting doses 3-5mg protein for cows milk, wheat, soy, hen s egg 8-10% first dose reactors for milk and hen s egg 0.5-1% at risk of severe reactions starting doses were 33 and 166-fold higher than VITAL Reference Doses for milk and egg respectively 24
Single dose challenges Concept Run in routine allergy clinics Challenge every patient attending for the food allergy of interest (no exclusions) Single dose ED05 selected as balance between good safety and numbers needed to be challenged for statistical robustness ED05 Open challenges Information generated for risk assessment Validation of ED05 derived from dose distribution modelling Severity profile at ED05 25
Single dose challenges: peanut study 375 clinic attendees with peanut allergy Three centres: Cork, Melbourne, Boston 6mg whole peanut in a cookie (except for participants allergic to other ingredients in the cookie) Open challenge 2-hour post-challenge follow-up Data support the VITAL ED05 value of 1.5mg for peanut protein Full results expected to be published soon! 26
Current developments in Europe
Chapter V. Article 36 3. The Commission shall adopt implementing acts on the application of the requirements referred to in paragraph 2 of this Article to the following voluntary food information: (a) information on the possible and unintentional presence in food of substances or products causing allergies or intolerances; 28
New requirements for voluntary allergen information (Reg 1169/2011) Precautionary labelling remains voluntary (Article 36) However mandatory requirements are introduced (e.g. name of allergenic food) Specific rules apply: 2. Food information provided on a voluntary basis shall meet the following requirements: (a) it shall not mislead the consumer, as referred to in Article 7; (b) it shall not be ambiguous or confusing for the consumer; and (c) it shall, where appropriate, be based on the relevant scientific data.
What could it all mean? (a) shall not mislead: PAL should be accurate, i.e. use must be justified (b)shall not be ambiguous or confusing: terminology should be clear and limited to one (or a few) well-understood terms (c) be based on the relevant scientific data: PAL should be based on a thorough risk assessment (preferably quantitative)
DG SANTE-JRC stakeholder workshop (Geel, Belgium 16-17 June 2016) Participants (46): Delegates (19) from Member States' competent authorities and delegates representing relevant stakeholders (e.g. FoodDrinkEurope and the European Federation of Allergy and Airways Disease Patients Association). AIMS (provided by DG SANTE-JRC) Background: Regulation (EU) 1169 /2011 on the provision of food information to consumers and the observed proliferation of precautionary allergen labelling by food producers. To identify the sequence of steps required for framing the current use of precautionary allergen information and its enforcement across the EU.
DG SANTE-JRC stakeholder workshop (Geel, Belgium 16-17 June 2016) Agenda SESSION 1: Legislative and Allergy Sufferers Requirements (DG SANTÉ, EFA) SESSION 2: Risk Based Approaches to Allergen Management (FoodDrinkEurope, ifaam) SESSION 3: The Role of Analysis in Enforcing Legislation (JRC-IRMM) Breakout groups after each session SESSION 4: Conclusions from Discussion Topics Topic 1: Legislative perspective on precautionary labelling, its current wording and conditions of use Topic 2: Risk based approaches Topic 3: Comparing results from analytical measurements
DG SANTE-JRC stakeholder workshop (Geel, Belgium 16-17 June 2016): Conclusions 1 Legislative perspective on precautionary labelling, its current wording and conditions of use. PAL terminology: should be simple, easy for consumers to understand may contain recommended Use of PAL should be subject to defined conditions and transparent: Documented risk assessment Allergen management procedures in place No PAL statement below reference dose Benchmarks need to balance degree of protection/safety and choice for allergic consumerss (reference doses) need endorsement by EFSA Communication to users (both consumers and health care practitioners) is crucial
DG SANTE-JRC stakeholder workshop (Geel, Belgium 16-17 June 2016): Conclusions 2 Risk-based approaches Guidance on good risk assessment practice EU-wide required Protein is the hazard and should be basis of the risk assessment Stakeholders want acceptance (by the authorities) of the RDs defined by VITAL They wish to encourage FBOs to use them and evaluate how well they work. Commission role to develop a framework based on general principles detail to be developed by other stakeholders (e.g. authorities, trade associations) Questions on readiness of FBOs for application of RDs (VITAL/iFAAM)
DG SANTE-JRC stakeholder workshop (Geel, Belgium 16-17 June 2016): conclusions 3 Comparing results from analytical measurements Expressed results in units that can be directly applied to the risk assessment, i.e. mg total protein/kg of food This links analysis to the materials used for clinical food challenges. Could be looked at in the context of Infrastructure to support framework: existing structures may provide a possible model e.g. Veterinary Medicines Priority allergens: wheat, milk and egg, based on frequency of RASFF notifications for these allergens Guidance to good analytical practice for food allergens should be developed Nordic group could lead, based on their experience Further workshops likely needed as work developed
Concluding remarks Precautionary allergen labelling (PAL) continues to fail allergic consumers All stakeholders accept that this can only be remedied by the definition and acceptance of thresholds for allergen management The VITAL 2.0 scheme proposed scientifically sound and transparent reference doses, based on a human data Developing scientific and regulatory perspectives offer opportunities to introduce a robust framework for the application of PAL Acting on these opportunities can restore the value of PAL and thereby help allergic consumers as well as FBOs
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