FDA to Assess Risk of Salmonellosis Associated with Eating ......1. Salmonella prevalence & concentration on tree nuts 2. Salmonella survival & inactivation on tree nuts during storage

Harris,L.J.UCDavis04/19/2016

Harris,LindaJ.,UCDavis 1

Linda J. Harris, Ph.D., CFSDepartment of Food Science and Technology

UC DavisApril 19, 2016

FDA tree nut risk assessment

FDA to Assess Risk of Salmonellosis Associated with Eating Tree Nutsp July 17, 2013

n The risk assessment will inform FDA policy and may be useful for owners and operators of tree nut processing plants and other postharvest facilities, among other stakeholders.

http://www.fda.gov/Food/NewsEvents/ConstituentUpdates/ucm361206.htm

FDA Tree Nut Risk Assessment

p The purpose of the risk assessment will be to quantify the public health risk associated with the consumption of potentially Salmonella contaminated tree nuts and to evaluate the impact of risk-based preventive controls on the risk of human salmonellosis arising from consumption of tree nuts.

http://www.fda.gov/Food/NewsEvents/ConstituentUpdates/ucm361206.htm

Rationale: Salmonella contaminated tree nuts are a concern

1. Outbreaks of salmonellosis have occurred, e.g.:- Raw almonds (2000/2001 & 2003/2004)- Pine nuts (2011)- Desiccated coconut (1999)

2. Product has been recalled due to Salmonella contamination, e.g.:- Pistachios (2009/2010) - Pine nuts (2011)- Walnuts (2010) - Macadamia nuts (2013)- Hazelnuts (2009, 2013)

3. Salmonella has been isolated from product during surveys, e.g.:- Almonds - Macadamia nuts- Cashew nuts - Walnuts- Brazil nuts - Pistachio nuts

4

For references: please see Federal Register Notice or contact the presenters

http://www.fda.gov /d ownl oa ds/ Fo od /Foo dScie nc eRe se arc h/Ris kSaf etyA sse ssm en t/UC M 36 229 7. ppt x

Risk assessment: The risk Assessment Framework

Conduct & Manage Process

Step 1: Commission

Step 2: Data collection & evaluation

Step 3: Develop model/reportStep 4: Review & clearance

Step 5: Issue

5http://www.fda.gov /d ownl oa ds/ Fo od /Foo dScie nc eRe se arc h/Ris kSaf etyA sse ssm en t/UC M 36 229 7. ppt x

Risk assessment: Choosing a quantitative approach• We anticipate the following model outputs:

- Expected number of cases / serving or cases / year- Quantified impact of interventions through

“what-if scenarios”

• Model likely based on peer-reviewed risk assessment models: – e.g. Lambertini et al., 2012 (developed for U.S. almonds)– Plan to evaluate product pathway: harvest to consumption

• Expected extensions beyond currently published models:– Adaptation to consider other tree nuts in addition to almonds– Quantification of uncertainty – Sensitivity analysis




Risk assessment: Proposed model outline

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Salmonella prevalence at harvest Salmonella concentration at harvest

Pre-process storage

Post-harvest treatment

Post-process storage

Retail storage

Consumer home storage

Risk of illness per annum & r isk per billion servings

Dose-Response model Serving size

Number of servings

http://www.fda.gov /d ownl oa ds/ Fo od /Foo dScie nc eRe se arc h/Ris kSaf etyA sse ssm en t/UC M 36 229 7. ppt x

Risk assessment: Data needs for modeling

1. Salmonella prevalence & concentration on tree nuts

2. Salmonella survival & inactivation on tree nuts during storage

3. Salmonella inactivation through post-harvest treatments

4. Salmonella dose-response relationships (we currently plan to use published Salmonella dose-response models)

5. Tree nut consumption in the U.S.


Data Request: Salmonellaprevalence and concentration

Example: Prevalence of Salmonella in 100-g Raw Almond Kernels With 95% Confidence Intervals (Wilson Score)

0

0.5

1

1.5

2

2.5

Prevalence(PercentPositive)

Total 14,949 samples

~1% positive

Danyluk et al., 2007; Bansal et al., 2010; Lambertini et al., 2012, unpublished

0123456789

10

2002 2003 2004 2005 2006 2013

MPN

/100

g

Year

Example: Levels of Salmonella in almonds per 100 g

Average level of Salmonella in 109 positive samples -----13 ± 14 MPN/1000 g

Danyluk et al., 2007; Bansal et al., 2010; Lambertini et al., 2012, unpublished

Receiving

PostharvestHandlingofPistachios

Pre-cleaner

Huller(peeler)

FloatTank

Dryer

Sinkers85%

Silo

Dryer

Floaters15% Silo



90.0%

10.0%

2.6%

15.0%

5.0%

25.0%

2.4%

50.0%

0.0% 20.0% 40.0% 60.0% 80.0% 100.0%

Sinkers

Floaters

Inshell (Edible) Ediblekernel Shell InedibleKernel

Harris calculations

p Average prevalencen Almonds (kernel):

p 0.98% (100 g; 95% CI, 0.83 to 1.2%; 137 of 13,972) n Almonds (inshell):

p 1.3% (100 g; 95% CI, 0.61 to 2.8%; 6 of 455) n Pecans (inshell):

p 0.95% (100 g; 95% CI, 0.70 to 1.3%; 44 of 4,641)n Walnuts (inshell):

p 0.14% (375 g; 95% CI, 0.054 to 0.35%; 4 of 2,903) n Pistachio (inshell)

p Sinker: 0.37% (100 g; 95% CI 0.21 to 0.67; 11 of 2,934)p Floater: 2.0% (100 g; 95% CI 1.3 to 3.0; 21 of 1,032)

Danyluk et al., 2007; Bansal et al., 2010; Lambertini et al., 2012; Davidson et al., 2015; Brar et al., 2016; Harris et al., in press; unpublished

Prevalence equivalent? Data Request: Salmonella survival, growth or inactivation

p Impacts of nut composition, water activity, storage temperature

p Different stages on farm-to-fork continuum n Impact of relative humidity during storage,

geographic region or seasonp In different foods made with tree nuts as

ingredients

SurvivalofSalmonelladuringstorageat23°C,4°C,and-20°Conalmondsandpistachios.

Kimber et al.,submitted to Journal of Food Protection

Allenrichmentswerepositive

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6

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Population(logCFU/g)

StorageTime(days)

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0 50 100 150 200 250 300 350


StorageTime(days)

SurvivalofSalmonelladuringstorageat23°C,4°C,and-20°Conalmondsandpistachios.

Kimber et al.,submitted to Journal of Food Protection

Allenrichmentswerepositive

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1

2

3

4

5

6

0 50 100 150 200 250 300 350


StorageTime(days)

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StorageTime(days)

Slopeofline=-0.15logCFU/monthSlopeofline=-0.24logCFU/month



Salmonella declineinpistachiosandalmonds(Harrislaboratory,varioussources)

Data set (23ºC) Reduction Rate (log CFU/day)

Reduction Rate (log per 30 days)

P-value

AlmondsS. enteritidis PT30:

171 days 0.0105 0.32 <2·10-16

365 days 0.0069 0.21 <2·10-16

560 days 0.0079 0.24 <2·10-16

Log 9 180 days 0.0055 0.16 2.5·10-07

Log 7 180 days 0.0071 0.21 4.6·10-09

Log 5 180 days 0.0083 0.25 3.8·10-09

Log 3 180 days 0.0068 0.20 5.7·10-08

Salmonella cocktail, 201 days 0.00929 0.28 <2·10-16

PistachioSalmonella cocktail 0.00513 0.15 1.4 ·10-7

Reduction ratesbased on the linear fit: log (CFU)= log (CFU)– rate* time

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1

2

3

4

5

6

0 100 200 300 400 500 600

Popu

lation

(lo

g CF

U/g)

Time (days)

75°F (24°C)

Survival of Salmonella on stored almonds

Kimber et al., 2012, Journal of Food Protection 75:1394–1403

FDA analysis of storage data

Santillana Farakos, S. M., R. Pouillot, N. Anderson, R. Johnson, I. Son, and J. Van Doren. 2016. Modeling the survival kinetics of Salmonella in tree nuts for use in risk assessment. Int. J. Food Microbiol. 227:41–50.

Santillana Farakos et al., 2016. Int. J. Food Microbiol. 227:41

Santillana Farakos et al., 2016. Int. J. Food Microbiol. 227:41 Santillana Farakos et al., 2016. Int. J. Food Microbiol. 227:41



Survival of Salmonella in tree nuts

Santillana Farakos et al., 2016. Int. J. Food Microbiol. 227:41

CalculatedReductionsofSalmonellaDuringStorage

Nuttype MethodWeeks(LogCFU Reduction)

1 4 12 52Almonds FDA 0.40 0.84 1.50 3.27

Harris 0.055 0.22 0.66 2.85Pistachios FDA 0.14 0.35 0.73 1.99

Harris 0.035 0.14 0.41 1.79Walnuts FDA 0.66 1.20 1.93 3.62

Santillana Farakosetal. ,2016.Int. J. FoodMicrobiol. 227:41-50.Kimberetal. ,2012, JournalofFoodProtection75:1394–1403.Lambertinietal. ,2012.FoodResearchInternational45:1166–1174.

FDAcalculations

• Uncertainty dimension– Median,mean,2.5%,97.5%

• Variability dimension– Includestandarddeviation

CalculatedReductionsofSalmonellaDuringStorageofAlmonds

Method UncertaintyWeeks(LogCFU Reduction)

1 4 12 52FDA 97.5% 0.33 0.72 1.31 2.88

Median 0.40 0.83 1.48 3.23Mean 0.40 0.84 1.50 3.272.5% 0.49 1.00 1.78 3.85

Harris 0.055 0.22 0.66 2.85

Santillana Farakosetal. ,2016.Int. J. FoodMicrobiol. 227:41-50.Kimberetal. ,2012, JournalofFoodProtection75:1394–1403.Lambertinietal. ,2012.FoodResearchInternational45:1166–1174.

Santillana

Farakosetal.,2016.Int.J.FoodMicrobiol.227:41-50.

Week1 Week52

FDA uncertainty analysis

p Prevalencep Survivalp Concentrationp Consumption amountp Treatmentp Treatment variability



Data request:Storage, handling and processingp Typical storage conditions

n Time, temperature, relative humidityn From harvest to processing

p Types of treatments used to reduce bacterian Frequency appliedn Process conditionsn Efficacy of treatments

p Storage conditions post treatmentp Handling practices that are typically

applied by the consumer

Process Validation

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0 5 10 15

log

CFU/

g

Treatment time (min)

TSA 6 0 ºCTSA 7 0 ºCTSA 8 0 ºC

05

101520253035

5.0-5.45.5-5.96.0-6.46.5-6.97.0-7.4

Freq

uenc

y (%

)

Log CFU/almond reduction

SE PT30 reduction on almonds treated with PPO

PPO September 2004 Blanching June 2005Oil Roasting June 2005

0.0

2.0

4.0

6.0

8.0

0.0 1.0 2.0 3.0 4.0 5.0

Log

CFU/

g

Treatment time (min)

240°F 250°F 260°F

Du, et al., 2010, J . Food Prot. Danyluk et al., 2005, J . Food Prot. Harris , et al., 2011, Food Res . Int.

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5 0

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5 0

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5 0

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5 0

Consumer StorageofTree Nuts(Leeetal.,2010)

Storagetime(weeks)

60.2% 36.9% 55.2%

RoomTemperature:23ºC Refrigerator:4ºC Freezer:-20ºC

Storagetime(weeks)Storagetime(weeks)

62.1% 46.1%34.2%

46.8% 10.5% 11.6%

% C

onsu

mer

s st

orin

g fo

r th

e sp

ecifi

ed

dura

tion,

am

ong

cons

umer

s st

orin

g at

the

spec

ified

te

mpe

ratu

re

Data request:Food consumption practicesp Frequency consumed by population

subgroupsp Frequency consumed raw by different

population subgroupsp Frequency with which tree nuts that have

undergone treatments are consumed by different population subgroups

p Serving sizes

Almond Risk Assessment

Lambertini, E., M. D. Danyluk, D. W. Schaffner, C. K. Winter, and L. J. Harris. 2012. Risk of salmonellosis from consumption of almonds in the North American market. Food Res. Int. 45:1166–1174.

AlmondRiskAssessment• InitialRiskAssessmentin2006helpedestablishtarget4-log

reductionforregulation

• Version2:FoodResearchInternational,2012

• ElisabettaLambertini(PostDoc),DonSchaffner(Rutgers),MichelleDanyluk(UFL),CarlWinter(UCD),LindaHarris(UCD)

• Significantmodificationof2006riskassessment:– added new prevalence data, recalculation of levels, assumes

mandatory treatment (with portions andvalidation dataused inmodel), new information onconsumer handling, updatedconsumption, reassessment of2001outbreak



Modelformat–@Risksoftware

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Population

logCFU/g

Sto rage Time (d ays)

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2 .0

Perc

ent p

ositi

ve 1

00 g

sa

mple

s

Harv es t y earHistogram of conc

Salmonella Concentration on almonds (MPN/100 g)

Rel

ativ

e fre

quen

cy

0 5 10 15 20

0.0

0.5

1.0

1.5

2.0

Selectpositiveornegativesampleandlevelbasedon8-yearsurvey.

Selectpre-processingstoragetime/tempbasedonindustrydata.Calculatedecline.

Selectprocessbasedonindustrydata.Determinereductionachievedinthatprocessbasedonvalidationdata.

Selectpost-processstoragetime/tempbasedonindustryandconsumerdata.Calculatedecline.

Selectamountconsumed(average31.5g(1gto100g)

DetermineillnessbasedonFAO/WHOdose-responsecurveforSalmonella.

Lambertinietal. ,2012

Salmonelladose-response model (WHO/FAO 2002)

Dose response

p There is no such concept as the “infectious dose”

p One cell can make you sick

p 1 cell = 0.02% prob of illness, 1/392 people

p DR modeln FAO/WHO 2002. Risk

assessments of Salmonellain eggs and broiler chickens.

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Pro

babi

lity

of

Ill

nes

s

Log CFU/serving

RiskAssessmentModelOutput– SingleRun100,000IterationsBaselineAssumptions


D. Percent untreated: 10%0.250.200.150.100.05

0-10 -8 -6 -4 -2 0 2 4 6

Log (cases/year)

Freq

uenc

y

B. Prevalence: 65%

0.250.200.150.100.05

0-10 -8 -6 -4 -2 0 2 4 6

Freq

uenc

y

Log (cases/year)

C. Concentration: 100 MPN/100g0.250.200.150.100.05

0-10 -8 -6 -4 -2 0 2 4 6

Freq

uenc

y

Log (cases/year)

A. Baseline

0.250.200.150.100.05

0-10 -8 -6 -4 -2 0 2 4 6

Freq

uenc

y

Log (cases/year)

RiskAssessmentModelOutput– SingleRun100,000Iterations


Summary

• FDAtreenut riskassessmentforalmonds isunder review– Unknownpublicationdate

• Riskassessmentscanbeusedtoinformriskmanagementdecisions– Exampleofmanagementdecisions

• Appropriatelevelofpathogenreduction• Criterionfor“pasteurized”label.



Questions?

Documents

FDA to Assess Risk of Salmonellosis Associated with Eating ......1. Salmonella prevalence & concentration on tree nuts 2. Salmonella survival & inactivation on tree nuts during storage