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

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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