Risk assessments on

Enterobacter sakazakii

(Cronobacter spp.) in

powdered infant formula

and follow-up formula

Sarah Cahill

Nutrition and Consumer Protection Division

Food and Agriculture Organization of the United Nations, Rome, Italy

Outline

� JEMRA

� E. sakazakii (Cronobacter spp.) in the

international standard setting arena

� International risk assessment work

� Outputs

� Conclusions

International

risk assessmentJECFA, JMPR, JEMRA,

ad hoc expert

consultations

Member Countries

Data, expertise

Scientific

advice

WTO Agreements

Benchmark

standards

Scientific

advice

International trade agreementsStandards,

guidelines,

related texts

Requests for

advice, risk

assessment

Needs,

feasibility,

inputs, etc.

International risk managerCODEX

ALIMENTARIUS

JEMRA

E. sakazakii (Cronobacter

spp.) in the international standard setting arena

� Urgency� High mortality in infants� Issue raised by countries in Codex meetings, World Health

Assembly

� Powdered infant formula (PIF) meeting the existing international/Codex standards implicated in cases of illness� Did not specifically address E. sakazakii

� How?

� micro criteria?� guidance for manufacturers?

� guidance for users?→ Needed a review of the science

→ Questions for the risk assessment

Challenges in undertaking an

international risk assessment

� Diversity in product and production systems

� Differences in preparation and use of product, exposure

� But

� Very specific product focus

� Product in international trade - from one plant product goes to many different countries

� Increased value of a global approach

Risk assessment

� 4 years (2003 – 2007)

� 35 + experts

� Review of scientific literature and approx 56 data submissions from around the world (national authorities, industry, academia, consumers)

� Initial focus – PIF, then FUF

Direct outputs

� 3 published reports (MRA 6, 10, 15)

� web-based risk assessment tool

Risk assessment in an

evolving environment

� 2003 – a handful of groups working on this organism 2009 – international conference

� Detection methods – evolving

� Sources of organism

� Evolving taxonomy – 2008 name change E. sakazakii to Cronobacter spp.

� Geographic extent of problem (lack of surveillance means this is still a limitation)

Impact on approach and

model design

� Flexibility

� Capable of coping with changes in

data or different data sets

� Facilitate “live” or “real-time” use and

rapid assessment of a range of

scenarios

Other challenges to model

development

� Lack of information on dose- response

� assumption that illness results from

presence of 1 cfu per serving in dry

PIF at time of preparation

� Focus on relative risk rather than

absolute risk

Other challenges to model

development

� Lack of information on variations in

preparation, storage and use of PIF

� survey undertaken by international

consumer body which identified the

variations that exist

� Information on preparation and use to

be input by the user of the model

Dose per ServingDose per Serving

DeclineDecline GrowthGrowth

Concentration In powder supply

Concentration In powder supply

Temperature of PIFTemperature of PIF

Number of CasesNumber of Cases

Impact of sampling plan

Impact of sampling plan

Concentration in powder supply

Concentration in powder supply

Relative RiskRelative Risk

Initial concentration

Initial concentration

Dose per servingDose per serving

Probability of illnessper contaminated serving

Probability of illnessper contaminated serving

Number of contaminatedservings

Number of contaminatedservings

Preparation scenarioPreparation scenario

Total PIF Consumption

Total PIF Consumption

Formula requirements

Formula requirements

Powder consumption

Powder consumption

Infant weightInfant weight

www.mramodels.org

What has this work allowed

us to do?

� Review of data

� PIF

� FUF

� Application of model

� PIF

Categorization of

microorganisms of concern

Cases of specified illness in infants

Identified pathogensConsumption of PIF

Salmonella

E. sakazakii

Category B

Pantoea agglomerans and

Escherichia vulneris

Hafnia alvei,

Klebsiella pneumoniae,

Citrobacter koseri,

Citrobacter

freundii,

Klebsiella oxytoca,

Enterobacter cloacae,

Escherichia coli, Serratia

spp. and Acinetobacter

spp.

Category C

Bacillus cereus, Clostridium difficile,

Clostridium perfringens, Clostridium

botulinum, Listeria monocytogenes,

Staphylococcus aureus and

coagulase-negative

staphylococci

Definition of at risk groups

� ~120 individually documented cases

among infants and young children < 3

years of age

� majority in <2 month olds

� 6 cases – 6 to 11 month age group

� 2 cases – 12 to 36 month age group

Definition of at risk groups

� Invasive cases in all age groups

� but infants at particular risk &

� neonates and infants under 2 months at greatest risk

� Caveats

• data from developed countries

• impact of an increase of risk factors which compromise immune system – definition may have to change

� Risk management implications

� focus on products for groups at greatest risk (PIF)

� how to address products for older infants (follow-up formula)

What has this allowed us to

do?

� Inform the revision of the Codex recommended code of hygienic practice – Adopted in 2008

� Establishment of new end product criteria for PIF

� Enterobacter sakazakii (Cronobacter species) n =30 c=0 m=0/10 g (2 class plan)

� Salmonella n=60 c=0 m=0/25 g

� Process hygiene criteria

Mesophilic Aerobic Bacteria c=5 n=2 m=500/g M=5000/g (3 class)

Enterobacteriaceae c=10 n=2 m=0/10 g (2 class)

Follow-up formula

� no clear scientific justification either for or against establishing a micro criterion for E. sakazakii in FUF

� Risk management outcome � No criteria established but if evidence in a

particular country of increased risk apply criteria for PIF

� Increased emphasis on consumer education re use of this product

� Encourage more data collection to clarify situation

What has this allowed us to

do?

� Highlight the impact in variations of

consumer practices

� important role of consumers

� need for education

� Greater emphasis on this in the

revised Codex guidelines

� Additional guidance by WHO and

FAO

Development of risk based

guidelines for the safe preparation, storage and use of PIF

Facilitated by the collaboration of

FSAI

Summary & conclusions

� E. sakazakii / Cronobacter heralded a new approach for addressing an emerging pathogen in an

� Communication and collaboration with and among research and academic community and industry

� Risk managers need to be the drivers of the risk assessment process

� Value of international risk assessment

� flexibility is key

� only as good as the decisions it allows risk managers to make (need to be a step ahead of risk managers)

� Conversion of risk assessment outputs into something practical...e.g. targeted guidance documents

Acknowledgements

Experts

Colin Block

Anna Bowen

Chris Braden

Robert Buchanan

Celia Carlos

Verna Carolissen

Bernard Coignard

Martin Cole

Paul Cook

John Cowden

Donald Campbell

Jean-Louis Cordier

Alexander Cravioto

Sue Dobson

Sri Estuningsih

Séamus Fanning

Jeffrey Farber

Aamir Fazil

Sara Fein

Stephen Forsythe

Mary Friel

Emma Hartnett

Arie Havelaar

Shizunobu Igimi

Judith Kellls

Daniel March

Jeronimas Maskeliunas

Harry Muytjens

Gopinath Balakrish Nair

Lisa Lefferts

Greg Paoli

Hildegaard Przyrembel

Alan Reilly

Caroline Smith Dewaal

Firdausi Qadri

Juliana Ruzante

Hajime Toyofuku

Jos Van Acher

Kaye Wachsmuth

Donald Zink

Marcel Zweitering

� Data providers (NGOs, Academic institutions, industry, National authorities)

� Resource providers (financial or in kind) –FAO, WHO, US, Japan, FSAI, FDA-CFSAN

� FAO and WHO – Maria de Lourdes Costarrica, Peter KarimBenEmbarek

http://www.fao.org/ag/agn/agns/jemra_index_en.asp

jemra@fao.org

Thank you