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
Deliberate presence
point in the food supply chain,
(Ingredients)
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
Two
scenarios
Unintended presence
(cross-contact, etc)
Ingredient
labelling
Allergen risk
management
Formulation,
traceability
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%
80%
70%
60%
50%
40%
30%
20%
10%
0%
Ben-Shoshan et al. JACI (2012) 129: 1401
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
PAL: 9 Annex II
foods
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
Risk Profile
75
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)
Concentration in a
Level of protection
50g serving
of RD
(“Action level”)
(mg/kg)
99
4.00
99
2.00
Peanut
Milk
ED01
ED01
0.20
0.10
Egg
ED01
0.03
99
0.60
Hazelnut*
ED01
0.10
99
2.00
Soy
95%LCI ED05
1.00
>95
20.00
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
•
Open challenges
ED05
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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