Anaphylaxis Campaign
Corporate Conference September 2017

Allergen control: the complete picture

Notes on the presentations by Michelle Berriedale-Johnson

Beyond then IFAAM study: what next for preventing and treating allergic reactions? – Professor Clare Mills, Manchester Institute of Biotechnology

Putting thresholds into practice – Dr René Crevel, René Crevel Consulting

Allergen Analysis – what should we consider when moving towards allergen thresholds – Pauline Titchener, Neogen

Thresholds and actions levels: a retailer's perspective – Juliette Jahaj, Sainsbury's

The TRACE peanut study – learning about thresholds to improve allergen labelling – Dr Shelley Dua, Addenbrookes Hospital

Keeping the allergic consumer safe – a view from the food service sector – Barry Moore, Performance Director, Gather & Gather

Some points from the Q&A/Panel discussion

Beyond IFAAM: what next for preventing and treating allergic reactions?
Professor Clare Mills, Manchester Institute of Biotechnology

IFAAM – Integrated Approach to Food Allergen and Allergy Management – is a Europe wide project designed to take forward the findings of the Euro Prevall work assessing the incidence and severity of food allergy across Europe.

A few of the findings of EuroPrevall that have informed the work of IFAAM:

• There is little uniformity in the incidence of allergy across Europe. So while cow's milk allergy affects 1% of the population in the UK or the Netherlands it scarcely exits in Greece.
• It is possible that latitude – maybe in terms of Vitamin D exposure – or different weaning procedures could account for some of the differences.
• Up to 80% of infants with milk or egg allergy had lost this by age 10; 50% of infants with peanut allergy were also clear by age 10.
• Breast feeding did not appear to equate with a low incidence of food allergy.
• Through all the groups early introduction of peanuts reduced the prevalence of allergy but, allergens do not always perform the same way and this did not apply to egg.
• IgE sensitisation did not appear to change with a reduction in the incidence of allergic reactions.
• The severity of the reaction did not appear to be directly linked with the threshold for the reaction.
• The role of the matrix (the foodstuff in which the allergen is eaten) is crucial in terms of the speed and severity of the reaction.
• The speed and severity of the reaction may also be affected by medications taken by the sufferer – such as anti-acids taken by 25% of the population.
• There is still insufficient data for some allergens (walnuts, Brazil nuts, some fish species, all molluscs and crustaceans) to establish viable thresholds.
• Establishing population thresholds for allergens depends on agreeing on an acceptable level of reaction eg a reaction which would only be experienced by 1–5% of the severely allergic population if they were to encounter that level of allergen.

IFAAM – Allergen Tool Management Box

The work of IFAAM is to use the findings of EuroPrevall to establish management tools for industry going forward.

• The tool box uses the Australian VITAL 2 allergen thresholds but in the context of consumption quantities, not portion size. (Working on portion size can be very misleading as portion sizes differ and individuals may consume more than one portion.)
• Knowing how much allergen is actually in the product depends on the quality of the tests available. The current ELISA tests remain hugely variable and although mass spectrometry testing is more accurate much development is still needed. (See Pauline Titchener's presentation below for more on testing.)
• Assessment of the matrix (the foodstuff) in which the allergen is appears is essential.
• References doses (whether no detectable level,1 part per million, 10 parts per million, 20 parts per million etc) vary across Europe which makes a uniform approach difficult.
• There is an urgent need to establish a way of informing the consumer via the label on the product that appropriate risk assessment has been done on a food and that it therefore conforms to the allergen protocols and is safe for them to eat. Viz: Precautionary Allergen labelling (PAL) which can be trusted.

Acceptable level of risk

However, for this work to go forward there is an urgent need to establish what consumers would regard as an 'acceptable level of risk'. Would tingling lips be acceptable while a drop in lung function would not be? Data is needed from sufferers to establish this but that data is is likely to prove in different parts of Europe and for different allergies.

New treatments

There are new treatments for allergy based on immunotherapy principles being developed both in France and the US (see this blog for more details) with yet more waiting in the wings. These will change the dynamics in food allergy treatment as they will move it beyond a purely food industry issue into the realms of the pharmaceutical industry with all the possible investment that might bring with it.

Putting thresholds into practice: where are we now?
Dr René Crevel, René Crevel Consulting

The path to thresholds

• In the late1980s, with the growth in the incidence of food allergy, it became a food safety issue.
• 1994 - ILSI (International Life Sciences Institute) established to find a level of allergen at which a reaction will be triggered.
• To identify risk and the to characterise it, Double Blind Food Challenges were used.
• 2009 – The establishment of the EuroPrevall programme (see above).
• 2011 – VITAL2 levels agreed.
• 2013 – Establishment of IFAAM (see above) to take the work forward.
• 2016 – At a European stakeholder meeting it was agreed to move forward combining the VITAL levels with the EuroPrevall/IFAAM work.

What is a threshold?

• Toxicologically a threshold is a dose below which a reaction will not occur.
• Regulatorily it is a level which will protect the vast majority of the relevant population: 20ppm of gluten for coeliacs for example.
• In allergen management terms, the threshold will probably be below the regulatory threshold. (Most manufacturers of gluten-free products, for example, aim for 5ppm or less even though the regulatory threshold is 20ppm.)

What constitutes a 'dose'? when it elicits -

• No reaction
• No objective reaction (one that can be measured as opposed to one that the sufferer feels)
• No severe reactions
• Only reactions which do not pose a risk to human health

So an 'eliciting dose' is a dose which you would expect to elicit a reaction in a percentage of the reactive population – probably aiming for 1–5% of that population.

Managing risk

• Managing risk starts with setting safe levels/doses as the dose is the only thing that you can control in the allergic person.
• Originally there was no data on thresholds or doses so it was decided to base labelling on presence only – either the allergen was there (in the ingredients) or it was not.
• But that did not deal with contamination. Hence the development of PAL - Precautionary Allergen/May contain Labelling
• PAL works well when proper risk assessment has been done on the product but is useless unless it has.

What is needed to put thresholds into practice?

• They need to be defined.
  VITAL 2 levels derived from food challenges have now been agreed. Anecdotally these appear to be safe although clinical evidence is needed to back them up.
• A level of tolerable risk has to be agreed - and tools need to be in place to achieve these standards throughout the food industry.
• This involves 'defining protection goals' as regards PAL. Establishing the 'risk' at the right level is essential. Set it too high and every food will carry a warning, set it too low and none will - both of which options damage credibility with the consumer.
• It is important to educate those whose risk falls outside the reference dose eg that 1–5% of the allergic population who will still react below the threshold.

Risk Assessment Toolkits

• Tier 1 – designed for SMEs and requires minimal knowledge and input from user. Simple set of yes/no answers which will raise a red alert if there is an issue.
• Tier 2 – more complex procedure for larger manufacturers and SMEs for whom a red alert has been raised at Tier 1.

Regulatory framework

Allergen management does fall with general food and food safety law which means that:

• Labelling should not mislead a customer – and this can include not doing a risk assessment
• It should not be ambiguous or confusing
• It should be appropriate and based on the relevant data - eg risk assessment

The European food safety group DG Santé (Directorate General for Health and Food Safety) further agreed in June 2016:

• Labelling should be simple, easy to understand and transparent
• That protection and safety as endorsed by EFSA (the European Food Safety Authority) should be paramount
• That stakeholders should accept the VITAL 2 reference doses
• That guidance was essential for all and that good communication with the consumer was vital

So where are we now?

• The thresholds are largely defined for all major food allergens
• Protection for the allergic consumer – we are getting there
• The toolkit – is effectively ready for use
• The regulatory framework is in place but, it is still only voluntary which dramatically limits its usefulness
• The acceptance by stakeholders is good.

Allergen Analysis – What we should consider when moving towards allergen thresholds
Pauline Titchener – Neogen

Considerations...

• VITAL Action Levels were based on portion sizes but portion sizes vary dramatically which can present analytical challenges. In smaller portions, for example, the levels of the allergic proteins may be below an analysable level.
• Analysis is only of finished products but the ingredients may already have been tested. Should that information be available?

The widely used Camden BRI Guide 71 for food allergens states that thresholds are not applicable where:

• 'Freefrom' is claimed
• Where it is an infant food for which there is no data
• Where a risk assessment has not been done
• Where there is no risk anyhow

Considerations when testing

• The physical nature of the product. If natural products – fruit, vegetable, cereals etc – the protein content of may vary depending on where, how and at what time of year it was grown; how ripe it is; whether it cross reacts with any other food which might give a false reaction etc etc
• Is it dispersible or a particulate? Does it run evenly through the product (milk in a sauce) or does it come in lumps (pieces of nut in a dessert)?
• The concentration of the allergen in the product may vary – so milk proteins in liquid milk, powdered milk, yogurt or cheese.
• Processing can have a significant effect on the protein content of the food. Roasting, fermentation, baking, frying, extrusion, hydrolization can all affect the proteins as can processing aids and additives.
• Sampling. Will the sample that a laboratory receives be representative of the whole? Wheat grains in oats for example might only appear in 5% of the total batch.
• Portion size remains challenging.
• It is not currently possible to test for either celery or molluscs.

Thresholds and and action levels: a retailer's perspective

Juliette Jahaj, Sainsbury's

As an allergy sufferer herself, Juliette Jahaj has a very personal interest in allergy and in the factories that she audits all over the world. But she also understands that allergy education is not necessarily as developed elsewhere in the world, where just having enough to eat is more of an issue than what is actually in the food. (She quoted one factory in India where her request for an ingredients list was greeted with the response – 'Ah but we are mean -– we don't give you the ingredients as well as the food – what do you think we are?')

The numbers of products being recalled because of allergy issues continues to go up but she believes that this has more to do with awareness than with an an actual increase in numbers. The vast majority of recalls continue to be for labelling errors.

However, there are areas where issues can arise. For example:

• Wheat flour is often contaminated with soya - this should be labelled
• Weevils in flour may appear harmless in allergen terms but they are in fact crustacea

She pointed out that consumer understanding of allergens and of labelling issues remains extremely low, even among invested parents of allergic children.

The TRACE peanut study – learning about thresholds to improve allergen labelling

Dr Shelley Dua, Cambridge Peanut Allergy Clinic, Addenbrookes Hospital

Dr Shelley Dua, who has just joined the consultancy team at the Peanut Allergy Clinic, has been closely involved with the TRACE (Thresholds of Reactivity And Clinical Evaluation) study which aims to evaluate the extrinsic factors which may be relevant in an allergic reaction. She took us through the thinking behind the study and an update on it so far.

What is a threshold?

• The amount of protein needed to provoke a reaction. But at what level should that be set at?
• ED10 – 3mg peanut protein – this is likely to provoke a reaction in 10% of the allergic population?
• ED1–ED5 – a far lower amount which only provoke a reaction i 1–5% of the allergic population
• But...
• Thresholds vary enormously – up to 10 fold – between individuals
• There is little information so far on the relationship between dose and severity of reaction

Why are there such wide variations between individual reactions?

'Host' factors – factors within each individual which may influence the severity of their reaction:

• If they suffer from asthma
• If they suffer from hay fever and the pollen count is high
• The severity of previous reactions
• If they have some other illness
• If they are taking medications
• Their age

'Extrinsic factors' – factors which might also affect the severity of their reaction

• If they are sleep deprived
• If they have been taking vigorous exercise
• If they have been drinking alcohol
• If they have some other infection
• If they are taking NSAIDs
• If they are stressed
• If the are a woman and they are menstruating

Immunotherapy studies had showed that patients tended to loose some of their allergen tolerance when they were either tired or exercising.

Why does this happen?

• Stress, sleep deprivation and exercise all cause the gut to be come more leaky allowing allergic proteins through the gut wall and into the blood stream.
• Stress and sleep deprivation can also stimulate mast cell activation which also causes the gut to become more leaky.

The objective of the TRACE study is to establish how much exercise/sleep deprivation was needed to affect that patient's reactivity.

TRACE study

64 peanut allergics took part in the study and were divided into three groups:

• One group just ate an increasing dose of peanut without any interventions.
• The second group was required to exercise at 80% capacity for 10 minutes before each increasing dose.
• The third group was only allowed to sleep for two hours each time before being woken and given their increased dose.

The study is only just complete so the detailed results are not yet available but Dr Dua could tell use that it was clear that both sleep deprivation and exercise had a significant effect on reactivity.

Keeping the allergic consumer safe – a view from the food service sector

Barry Moore, Performance Director, Gather and Gather

As the father of a peanut allergic boy and the performance director for a large catering company, Barry understands the problems of allergy in food service better than most.

And his is aware that an estimated 25% of allergic consumers do have a reaction when they eat out, often when they eat in fast food outlets.

There are major inherent problems with dealing with allergies in food service:

• It is a massive industry employing 2.9 million people – the fourth largest employer in the country.
• There is a very rapid turnover of staff for many of whom English is not their first language.
• There is an inherent risk of cross contamination in any outlet which deal both with allergens and with allergen free food.
• There is a more or less total lack of understanding and awareness of allergy among operatives unless they have seen the consequences in person.
• When an allergy incident occurs, especially if that is a fatality, it has a dramatic and life changing effect not only on the family of the person affected but on the operative and his/her family who may have been responsible, even if unwittingly, for the allergy issue.
• So raising awareness is crucial.

This is the point of the AC's new campaign – Ask the Question

Ask the Question will follow the format of the campaign's enormously successful #Take the Kit campaign which included this incredibly hard hitting film and which highlighted the importance of always carrying your adrenaline injector pen with at all times. (If you have never seen the film, please watch it.)

Ask the Question will focus on always asking about allergens in a catered situation and the consequences of not doing so.

The AC are looking for funding now, so if you think you can help, do contact CEO Lynne Regent – she will be more than happy to hear from you.

Some points from the Q&A/Panel discussion

• Personal allergy test kits were given the thumbs down by all panel members: dangerous and inaccurate.
• What should the levels be for a 'freefrom' claim? Undetectable? The lowest possible level? An acceptable adverse reaction level? NB. For hydrolised infant formula the acceptable adverse reaction level is 10%.
• In the UK the VITAL2 peanut reference dose is already being used but that needs to be universal across Europe. Patient organisations can help to push this forward.
• There is a worrying dearth of both medical and food researchers coming through – Dr Dua who has just been made a consultant is still one of only 11 adult allergy consultants in the country.
  It is possible the the increasing numbers of allergy sufferers may push more people into professions but there is a real need for government encouragement in this area.
• Airlines and peanuts. Opinion is divided, as with peanut free schools. Risk is inherent in an allergic person’s life and the most important thing for them to learn is how to deal with it. Risk free areas do not help them to do so.
  There is also very actual data on peanut risk in an aeroplane environment.
• VITAL thresholds appear to be safe so far but there is no evidence that they are – but neither is there any evidence that they are not.
  In Japan there has been a blanket 10mg/kilo threshold for all allergens for some years but there is no data available on reactions. This is now being revised which may provide more information.
• Food allergens are very difficult to measure – it is far easier to measure a pesticide! More government investment is needed in this area.

September 2017

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