MANAGING RISK IN THE “FREE-FROM”
SECTOR: HOW CAN MANUFACTURERS AVOID PUTTING
CONSUMERS, AND THEMSELVES, AT RISK
Understanding the “free-from” supertrend Food Matters; London 18-20 November 2014
René Crevel
OUTLINE
• What is meant and understood by “free-from”?
• Risk assessment: a critical requirement
• Evolution and development of risk assessment for
allergens
• Translation to “Free-From” products
• Conclusions
WHAT IS UNDERSTOOD BY “FREE-
FROM”? • “Free-from”: not subject to (or affected) by
(something undesirable) – Oxford Dictionaries online
• Motivation for seeking and using “free-from” products
varies
• Ethical
• Health or health perception of some food constituents
• Safety/nutritional imperative
• Etc
• The consequences of not achieving “free-from” status
differ quite drastically for the users
WHAT IS “FREE-FROM” IN PRACTICE?
• Zero is a very low number (Steve Taylor, FARRP)
• In practice, “free-from” does not (and cannot) denote
total absence
• Gluten 20mg/kg (1981<500ppm) (and 20ppm is not a No Effect Level)
• Lactose 100mg/kg (in many European countries)
• Allergens ???????
• Possibly the biggest challenge
• For people with food allergies, “free-from” is NOT
a lifestyle or ethical choice
• It can be a matter of life and death
• So if you are making an
allergen “free-from” claim,
it is critical to be able to
decide what makes the
difference between safe
and unsafe
ALLERGENS AND “FREE-FROM”
• Analytical methods still very much at developmental
stage
• Uncertainty about thresholds/minimum eliciting doses
• No agreement among regulators yet
• Perceived unpredictability of allergic reactions
How can we define “free-from” and provide
products which the exquisitely food-allergic can
trust?
First step is a thorough quantitative
assessment of the risk
RISK ASSESSMENT OF ALLERGENIC FOODS: EVOLUTION – A 20-YEAR JOURNEY
Early 1990s Nordic list
1995 FAO-WHO consultation – Codex List (1999)
1997 Peanut threshold study (Hourihane et al)
1999 1st Threshold conference
2002 Dose-distribution feasibility (Bindslev-Jensen et al)
2007 Considerations on use and interpretation of
dose-distribution data (Crevel et al)
2008 FDA Threshold Working Group: “the quantitative
risk assessment-based approach provides the strongest,
most transparent scientific analyses to establish thresholds
for the major food allergens”
2009 Europrevall-FSA workshop (Madsen et al)
2011 VITAL Scientific Expert Panel
2012 ILSI-Europe “Thresholds to Action Levels”
workshop
2014 ILSI-Europe “Severity vs dose” Expert Group
Hazard
identification
Hazard characterisation
Risk
assessment
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9
…… PRECAUTIONARY (ADVISORY –
“MAY CONTAIN”) LABELLING
• Introduced in the 1990s
• First suggested by CFIA/Health Canada
• Voluntary
• Very high level of precautionary labelling in
some food categories
BUT
• No clarity about standards for application:
use dependent on internal company standards
and perception of risks
• Negative perception by consumers and
health care practitioners
• Result: misunderstanding and mistrust,
lack of observance and consequently
higher risks to allergic consumers
1 Annex II
food
10 Annex II
foods
1
0
SO, PRECAUTIONARY (ADVISORY)
LABELLING…
• … on its own is not a definitive answer
• needs standards to ensure consistent application
• needs to communicate clearly the risk message to
allergic consumers
• needs to be used sparingly if it is to retain credibility and
effectiveness
• Current implementation doesn’t do this, hence the drive
for better, more refined assessment of allergen risks
1
1
ASSESSING ALLERGEN RISKS
• Focus of development of risk assessment approaches
has been on standards for precautionary allergen
labelling (“may contain”)
• However, knowledge gained and lessons learned can
also be usefully deployed in developing standards for
“free-from” specific allergens
• Indeed the US-FDA’s reasoning for adopting a 20ppm
limit for “gluten-free”, rather than a lower one is very
similar to the reasoning behind PAL
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RISK
Fundamental principle of toxicology:
“The dose makes the poison” (Paracelsus, 15th Century)
Implication: the key parameter is risk not hazard
Risk » the likelihood that, under particular conditions of exposure, an
intrinsic hazard will represent a threat to human health.
» Risk = f (hazard, exposure)
with a consideration of the nature of the effects
This applies as much to allergens as to other substances, although it has taken the best part of 20 years to be accepted
FOOD ALLERGENS: DOSE IS CRITICAL
INCREASING DOSE
Lip tingling, Itch Rash, hives
Nausea, vomiting, shortness of breath
Cardio-respiratory symptoms, severe angioedema, anaphylaxis
Probability of no or slight
effect
Probability of severe effect
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FOOD ALLERGENS: CHALLENGE DOSE AND DISTRIBUTION OF POPULATION RESPONSES
ED10 (mg) ED05 (mg)
Dose Lower 95% CI Dose Lower 95% CI
17.6 9.2 5.8 2.7
LOAEL: 0.5mg
ED10
VOLUNTARY INCIDENTAL TRACE
ALLERGEN LABELLING (VITAL)
• Originally developed under the aegis of the Allergen Bureau of
Australia-New Zealand (VITAL 1.0, 2007)
• Key innovation was definition of quantitative benchmarks (action
levels) for precautionary labelling
• Comprehensive review of VITAL scheme started in 2011
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• Panel of recognised and
independent international
external experts (chaired by
Prof Steve Taylor (FARRP,
University of Nebraska) to
revise and update action levels
based on most recent science
http://allergenbureau.net/vital/
VITAL SCIENTIFIC EXPERT PANEL: MODUS OPERANDI
• Keep original VITAL design principles: • Applies to foods for normal consumption
• Not designed for “specific allergen-free” foods
• Not designed for extremely reactive
• Although would provide protection in many cases
• Derive reference doses using dose distribution modelling
• Level of protection
» Panel decided to • Use ED01 where possible as the basis for reference doses,
providing a minimum protection factor of 99%
• Use lower 95% CI of ED05 where data were insufficient to use ED01
• Aim to protect vast majority against mild objective reactions
SEAC 16
ALLERGENS ANALYSED BY VITAL
SCIENTIFIC EXPERT PANEL
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Celeriac/celery
Fish
Lupine
Sesame seed
Shrimp
Soybean
Wheat
Cashew
Mustard
Peanut
Milk
Egg
Hazelnut
Assembled and evaluated clinical data on almost all priority
allergenic foods on the EU list
No data at all:
Molluscs
PEANUT DOSE DISTRIBUTION:
ADULTS AND CHILDREN COMBINED
SEAC 18
Cum
ula
tive P
erc
enta
ge o
f R
esponses
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Log-Normal Dose of Protein (mg)
0.01 0.1 1 10 100 1000 10000 100000
Discrete Cumulative
ED 01
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VITAL SCIENTIFIC EXPERT PANEL RECOMMENDATIONS AND PROPOSED ACTION LEVELS.
Allergen
No of
data
points
Basis of
reference dose
Reference
dose
(mg Protein)
50 g Serving
Size: Action
Level (ppm)
250 g
Serving Size:
Action Level
(ppm)
Peanut 750 ED01 0.20 4.0 0.80
Milk 351 ED01 0.10 2.0 0.40
Egg 206 ED01 0.03 0.6 0.12
Hazelnut 202 ED01 0.10 2.0 0.40
Soy 80 95%LCI ED05 1.00 20.0 4.00
Wheat 40 95%LCI ED05 1.00 20.0 4.00
Cashew 31 95%LCI ED05 2.00 40.0 8.00
Mustard 33 95%LCI ED05 0.05 1.0 0.20
Lupin 24 95%LCI ED05 4.00 80.0 16.00
Sesame 21 95%LCI ED05 0.20 4.0 0.80
Shrimp 48 95%LCI ED05 10.00 200.0 40.00
Celery 39 Insufficient data
Fish 19 Insufficient data
CONCLUSIONS OF THE VSEP
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The VITAL reference values, also adopted by the ILSI Expert Group “Thresholds to Action Levels” provide a high level of protection to allergic consumers:
• will protect a minimum of 95-99% of allergic consumers against mild objective reactions
• reactions in the more sensitive individuals are likely to be mild, transitory objective reactions typically requiring no pharmacological intervention
They are transparent and can be used to communicate risk meaningfully to allergic consumers and health care practitioners
They provide a consistent standard for precautionary labelling across industry, which can drive
• Improved allergen management
• Improved consumer safety
SEAC 21
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
WHAT DO THESE REFERENCE
DOSES MEAN? THE CLINICAL
DATA (3)
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• 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
MOVING FORWARD
• The ILSI-Europe Food Allergy Task Force
Expert Group “Thresholds to Action
Levels”
• The ILSI “Thresholds to Action Levels”
workshop Reading 13-14 September 2012
SEAC 23
CONCLUSIONS ENDORSED BY THE
WORKSHOP PARTICIPANTS
• A transparent set of reference doses (as a basis for action levels) would be a desirable outcome, in principle.
• Data from food challenge studies provide the appropriate foundation from which these action levels can be derived
• Sufficient data exist to move forward and better estimate the risk to the allergic population for the allergens specified in the report
• The proposed reference doses, based on the work of the VITAL Scientific Panel, constitute a reasonable first pass to minimise risk to the allergic consumer while maintaining food choices
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“FREE-FROM”: HOW CAN WE TRANSLATE RISK ASSESSMENT KNOWLEDGE
• Action Levels and Reference Doses are critical to the concept of “free-from”, but are they the threshold for “free-from”
• NO, because they have been developed to apply to everyday foods, manufactured using everyday sanitation processes, etc
• WHY?
• The Reference Doses are NOT No Effect Levels
• “Free-from” are specially prepared for and used by people who are at the very sensitive end of the spectrum and enhanced procedures need to be used to ensure that the risk remains low
• However they can be used as a benchmark
SEA
C 25
“FREE-FROM”, ALLERGEN MANAGEMENT
AND PUBLIC HEALTH OUTCOMES
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Allergen management
controls managed, with
unavoidable traces present
despite efforts
Allergen analytically
absent to a high degree of
confidence, GMPs to
ensure absence of
specific allergen
AMOUNT OF ALLERGENIC PROTEIN
Allergen management
cross-contact control
well-managed to a low
level
MANAGEMENT
PARAMETER
Lower limit of
analytical
detection
Action
Level
lower higher
Manufacturing facility “IN CONTROL”
“FREE
FROM”
“MAY CONTAIN”
“NOT SUITABLE FOR” “SUITABLE
FOR”
No reactions In the vast
majority of allergic
Individuals
No severe reactions in the
vast majority of allergic
individuals
No mild reactions in the
vast majority of highly
sensitive allergic
Individuals
PUBLIC
HEALTH
OUTCOME
ALLERGEN
STATUS
Ward R, Crevel R, Bell I, Khandke N, Ramsay C, Paine S. A vision for allergen
management best practice in the food industry. Trends Food Sci Tech 21 (2010) 619-
625.
CONCLUDING REMARKS
• Effective definition of “free-from” hinges on a good
understanding of allergen risks, grounded in quantitative
approaches
• Considerable progress has been made in developing and
using methodologies to assess allergen risks in general
allergen management, in particular for the application of PAL
• Translation of this knowledge will enable the development of
robust quantitative benchmarks for the design and operation
of facilities to supply products “free-from” specific allergens
with a high assurance of safety.
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THANK YOU FOR YOUR ATTENTION