The Role of Predictive The Role of Predictive Microbiology in Microbial Risk Microbiology in Microbial Risk AssessmentAssessment
Robert L. BuchananRobert L. BuchananU.S. DHHS Food and Drug U.S. DHHS Food and Drug AdministrationAdministration
Center for Food Safety and Applied Center for Food Safety and Applied NutritionNutrition
Microbiological Risk Microbiological Risk AssessmentAssessment
Microbial Risk AssessmentMicrobial Risk Assessment
Dramatic changes are occurring Dramatic changes are occurring in the way regulatory issues in the way regulatory issues associated with microbiological associated with microbiological foods safety concerns are foods safety concerns are evaluated as a result of the evaluated as a result of the emergence of quantitative emergence of quantitative microbial risk assessment microbial risk assessment techniques during the past 8 techniques during the past 8 years years
Microbial Risk AssessmentMicrobial Risk Assessment Prior to 1995:Prior to 1995: Generally considered Generally considered
that microbiological food safety that microbiological food safety concerns were too complex to be concerns were too complex to be amenable to formal risk assessment amenable to formal risk assessment techniquestechniques
1994 - 1996:1994 - 1996: First “research” First “research” attempts to conduct microbiological attempts to conduct microbiological risk assessments are publishedrisk assessments are published
1998:1998: First “formal” assessment First “formal” assessment conducted by a U.S. regulatory agency conducted by a U.S. regulatory agency publishedpublished
Barriers to Conducting Barriers to Conducting Microbial Risk AssessmentsMicrobial Risk Assessments
Large variation in virulence of strainsLarge variation in virulence of strains Large variation in susceptibility of hostsLarge variation in susceptibility of hosts Microbial populations change rapidly due Microbial populations change rapidly due
to growth and inactivationto growth and inactivation Large variation in growth and survival Large variation in growth and survival
characteristics of microorganismscharacteristics of microorganisms Microbial contamination sporadicMicrobial contamination sporadic Substantial amount of data on adverse Substantial amount of data on adverse
effects, but dose-response relations effects, but dose-response relations generally not establishedgenerally not established
Examples of Early Examples of Early “Research” Microbial Risk “Research” Microbial Risk AssessmentsAssessments
Drinking Water & Shellfish:Drinking Water & Shellfish: U.S. U.S. EPA; 1988 - 1996 (Rose, Gerba, EPA; 1988 - 1996 (Rose, Gerba, Haas)Haas)
Salmonella Salmonella Enteritidis - Eggs:Enteritidis - Eggs: USDA; USDA; 1996 - 1998 (Buchanan & Whiting; 1996 - 1998 (Buchanan & Whiting; Baker et al.) Baker et al.)
Listeria monocytogenesListeria monocytogenes:: FDA, FDA, USDA, ICMSF; 1994 - 1999 (Peeler & USDA, ICMSF; 1994 - 1999 (Peeler & Bunning; Miller et al.; Buchanan et Bunning; Miller et al.; Buchanan et al.; Whiting et al.)al.; Whiting et al.)
E. coliE. coli O157:H7 in Ground Beef: O157:H7 in Ground Beef: Health Canada, USDA; 1998 - 1999 Health Canada, USDA; 1998 - 1999 (Cassin et al.; Marks et al.) (Cassin et al.; Marks et al.)
U.S. Microbiological Risk U.S. Microbiological Risk AssessmentsAssessments Listeria Listeria
monocytogenesmonocytogenes in in ready-to-eat foodsready-to-eat foods
SalmonellaSalmonella Enteritidis in Eggs Enteritidis in Eggs and Egg Productsand Egg Products
Vibrio Vibrio parahaemolyticusparahaemolyticus in Oystersin Oysters
Listeria Listeria monocytogenesmonocytogenes in Deli Meatsin Deli Meats
EnterohemorrhagEnterohemorrhagic ic Escherichia coliEscherichia coli in Ground Beefin Ground Beef
Fluoroquinolone Fluoroquinolone Resistance in Resistance in CampylobacterCampylobacter
FAO/WHO Microbial Risk FAO/WHO Microbial Risk AssessmentsAssessments
Listeria Listeria monocytogenesmonocytogenes – – ready-to-eat foodsready-to-eat foods
SalmonellaSalmonella in in broilersbroilers
SalmonellaSalmonella Enteritidis in eggsEnteritidis in eggs
CampylobacterCampylobacter in in broilersbroilers
Vibrio Vibrio parahaemolyticusparahaemolyticus in fish and shellfishin fish and shellfish
Enterohemorrhagic Enterohemorrhagic Escherichia coliEscherichia coli in in ground beef and ground beef and produceproduce
What Is Microbial Risk What Is Microbial Risk Assessment?Assessment? Quantitative Quantitative
microbial food safety microbial food safety risk assessment is a risk assessment is a group of modeling group of modeling techniques that allow techniques that allow one to describe the one to describe the relationships between relationships between the presence of a the presence of a hazard in a food and hazard in a food and the likelihood that the likelihood that the hazard will lead the hazard will lead to an adverse public to an adverse public health consequence health consequence
What Is Microbial Risk What Is Microbial Risk Assessment?Assessment?
Risk assessments are a means of Risk assessments are a means of systematically arraying and analyzing systematically arraying and analyzing scientific data that are pertinent to a scientific data that are pertinent to a risk management question:risk management question: StructuredStructured
• to clearly tell what we knowto clearly tell what we know DescriptiveDescriptive
• to characterize how well we know itto characterize how well we know it TransparentTransparent
• to reveal any biasto reveal any bias
What Is Microbial Risk What Is Microbial Risk Assessment?Assessment? The end products of a risk The end products of a risk
assessment are:assessment are: a statement of probability or a statement of probability or
likelihoodlikelihood a statement of uncertainty.a statement of uncertainty.
Microbial Risk Microbial Risk AssessmentAssessment
QualitativeQualitative Probability and uncertainty are Probability and uncertainty are
expressed using descriptor (e.g., low expressed using descriptor (e.g., low risk, high risk)risk, high risk)
Used when eitherUsed when either• Insufficient data to describe risk Insufficient data to describe risk
quantitativelyquantitatively• Insufficient time, resources, or need to do a Insufficient time, resources, or need to do a
full risk assessmentfull risk assessment Many qualitative risk assessment are Many qualitative risk assessment are
actually semi-quantitativeactually semi-quantitative
Microbial Risk Microbial Risk AssessmentAssessment
QuantitativeQuantitative Provides an quantitative estimate Provides an quantitative estimate
of riskof risk• Single point estimateSingle point estimate• Probability profileProbability profile
Done using mathematical modeling Done using mathematical modeling Simple as possible and still answer Simple as possible and still answer
the risk management question the risk management question adequatelyadequately
Microbial Risk Microbial Risk AssessmentAssessment Flexible tool:Flexible tool:
Different typesDifferent types• Risk RankingRisk Ranking – priority setting – priority setting• Product/Pathogen Pathway AnalysisProduct/Pathogen Pathway Analysis – –
intervention strategiesintervention strategies• Risk-RiskRisk-Risk – examination of – examination of
consequencesconsequences• GeographicalGeographical – emergence – emergence
Address all or part of the food chainAddress all or part of the food chain
Microbial Risk Microbial Risk AssessmentAssessment
While specific techniques will vary While specific techniques will vary with the agent be examined, risk with the agent be examined, risk assessments are typically divided assessments are typically divided into four phasesinto four phases Hazard IdentificationHazard Identification Exposure AssessmentExposure Assessment Hazard Characterization (Dose-Hazard Characterization (Dose-
Response Relation + Severity Response Relation + Severity Assessment)Assessment)
Risk Characterization Risk Characterization
Why Dramatic Change?Why Dramatic Change?
InternationallyInternationally WTO SPS and TBT WTO SPS and TBT
AgreementsAgreements Codex Codex
AlimentariusAlimentarius Nationally (U.S.)Nationally (U.S.)
Executive OrderExecutive Order 1994 USDA 1994 USDA
Reorganization Reorganization Act Act
Why Dramatic Change?Why Dramatic Change?
Availability of Availability of personal personal computerscomputers
Availability of Availability of PC-based PC-based software for software for simulation simulation modelingmodeling ““Monte Carlo” Monte Carlo”
TechniquesTechniques
Why Dramatic Change?Why Dramatic Change?
10-year worldwide 10-year worldwide investment in investment in research in research in predictive predictive microbiologymicrobiology Modeling techniquesModeling techniques ModelsModels ExpertiseExpertise TrainingTraining Application software Application software
Predictive MicrobiologyPredictive Microbiology
Predictive MicrobiologyPredictive Microbiology
The use of The use of mathematics to mathematics to describe the describe the behavior of behavior of microorganismsmicroorganisms
1,000,000
Predictive MicrobiologyPredictive Microbiology
Emergence Emergence during the during the 1930’s as a 1930’s as a means of means of describing the describing the inactivation of inactivation of microorganisms microorganisms during thermal during thermal processingprocessing
Thermal Death Time Curve
D = -1/slope
Log #
Time
Predictive MicrobiologyPredictive Microbiology
Expanded greatly during the Expanded greatly during the 1980’s and 1990’s to include 1980’s and 1990’s to include modeling of modeling of GrowthGrowth SurvivalSurvival InactivationInactivation CompetitionCompetition Food Unit OperationsFood Unit Operations
Predictive MicrobiologyPredictive Microbiology
The availability of predictive The availability of predictive microbiology models are critical to microbiology models are critical to quantitative microbiology risk quantitative microbiology risk assessmentassessment
Usually “hidden”Usually “hidden” Mathematical expressions are imbedded Mathematical expressions are imbedded
in the risk assessment modelin the risk assessment model Need to look at the details of the risk Need to look at the details of the risk
assessmentassessment
Understanding Exposure Understanding Exposure AssessmentsAssessments
Risk is Risk is based on based on what goes what goes into the into the consumerconsumers’ mouths’ mouth
Understanding Exposure Understanding Exposure AssessmentsAssessments
Essentially all microbiological Essentially all microbiological data on the frequency and data on the frequency and extent of microbiological extent of microbiological contamination is collected at contamination is collected at sites earlier in food chainsites earlier in food chain
Predictive microbiology to Predictive microbiology to estimate the actual level estimate the actual level ingested by the consumeringested by the consumer
FDA FDA Listeria Listeria monocytogenesmonocytogenes Risk Risk AssessmentAssessment
Most data available on the Most data available on the various foods considered were various foods considered were “at retail”, with some critical “at retail”, with some critical databases at point of databases at point of manufacturermanufacturer
Need to take retail data and Need to take retail data and convert to “time of convert to “time of consumption” dataconsumption” data
Listeria monocytogenesListeria monocytogenes Exposure AssessmentExposure Assessment
Frequency of contamination of Frequency of contamination of foodfood
Number of Lm when contaminatedNumber of Lm when contaminated
Growth before Growth before consumptionconsumption
Frequency of Frequency of consumptionconsumption
Amount food Amount food consumedconsumed
Number of Lm consumed with a Number of Lm consumed with a servingserving
FDA FDA Listeria Listeria monocytogenesmonocytogenes Risk Risk AssessmentAssessment
To estimate exposure needed to To estimate exposure needed to have data and models forhave data and models for Food consumptionFood consumption Food contamination Food contamination Growth, survival and thermal Growth, survival and thermal
inactivation -- refrigeration, inactivation -- refrigeration, storage, and cooking/reheating storage, and cooking/reheating
Growth ModelGrowth Model
SqRT EGR = a ( T - To )SqRT EGR = a ( T - To )
Ratkowsky et al., 1982Ratkowsky et al., 1982
0.0
0.1
0.2
0.3
0.4
-5 0 5 10
Temperature (°C)
Sq
Rt
EG
R
(lo
g/d
)
Dealing with DiversityDealing with Diversity
0
5
10
15
20
25
30
<32 33-35 36-38 39-41 42-44 45-57 48-50 51-53 54-56 57-59 60-63
Home Refrigerator Temperatures (°F)
Semi-Soft Cheese
-0.005
0
0.005
0.01
0.015
0.02
0.025
0.03
0.035
0.04
0 5 10 15 20 25 30
Storage (Days)
Pro
bab
ility
Den
sity
Dealing with Diversity
Dealing with DiversityDealing with Diversity
00.10.20.30.40.50.60.70.80.9
1
0 0.2 0.4 0.6
Growth rate (log/d)
Cu
mu
lati
ve
Fre
qu
en
cy
Multiple Studies with Growth Data Adjusted to 5°CMultiple Studies with Growth Data Adjusted to 5°C
Mathematical ModelingMathematical Modeling
Use Monte Carlo simulations to Use Monte Carlo simulations to increase the accuracy of the increase the accuracy of the predictionspredictions
Considers parameters as Considers parameters as distributions instead of single distributions instead of single valuesvalues
Based on the “Theory of Large Based on the “Theory of Large Numbers”Numbers”
Monte Carlo SimulationMonte Carlo Simulation
What What number number would I get if would I get if I rolled three I rolled three dice?dice?
Monte Carlo SimulationMonte Carlo Simulation
33 33 11 = 7= 7
Monte Carlo SimulationMonte Carlo Simulation
66 66 33 = 15= 15
Monte Carlo SimulationMonte Carlo Simulation
0
5
10
15
20
25
30
0 5 10 15 20
Sum
Fre
quency
Mean = 10.5
FDA FDA Listeria Listeria monocytogenesmonocytogenes Risk Risk AssessmentAssessment
Example 1: Deli (Processed) Example 1: Deli (Processed) meats that support growth meats that support growth Manufacturer to Retail: Growth Manufacturer to Retail: Growth
rate model - temperaturerate model - temperature Retail to ConsumptionRetail to Consumption
• Growth rate model – temperatureGrowth rate model – temperature• Maximum growth model - temperatureMaximum growth model - temperature
FDA FDA Listeria Listeria monocytogenesmonocytogenes Risk Risk AssessmentAssessment
Example 2: Frankfurters Example 2: Frankfurters Manufacturer to Retail: Growth Manufacturer to Retail: Growth
rate model - temperaturerate model - temperature Retail to ConsumptionRetail to Consumption
• Growth rate model – temperatureGrowth rate model – temperature• Maximum growth rate model – Maximum growth rate model –
temperaturetemperature Food preparation: Thermal inaction Food preparation: Thermal inaction
modelsmodels• Percentage eaten without reheatingPercentage eaten without reheating
FDA FDA Listeria Listeria monocytogenesmonocytogenes Risk Risk AssessmentAssessment
Example 3: Example 3: Cultured Dairy Cultured Dairy Products Products Retail to Retail to
ConsumptionConsumption• Survival model – Survival model –
temperature and temperature and pHpH
Impact of Risk Assessment Impact of Risk Assessment on Predictive Microbiologyon Predictive Microbiology The lessons learned about variability and The lessons learned about variability and
uncertainty from risk assessment has greatly uncertainty from risk assessment has greatly expanded our knowledge, techniques, and expanded our knowledge, techniques, and tools that we use in predictive microbiologytools that we use in predictive microbiology
05
1015
Incubation Time (hr)
2.0
2.5
3.0
3.5
Lo
g (
Ba
cte
ria
l C
ou
nt)
SummarySummary Predictive microbiology and microbial Predictive microbiology and microbial
risk assessment are intimately risk assessment are intimately interconnectedinterconnected Cannot do risk assessment with predictive Cannot do risk assessment with predictive
microbiology modelsmicrobiology models Cannot understand predictive microbiology Cannot understand predictive microbiology
models without understanding of variability models without understanding of variability and uncertaintyand uncertainty
An investment in one will aid the advancement An investment in one will aid the advancement of the otherof the other
Part of an overall evolution in food safety Part of an overall evolution in food safety microbiology toward being more quantitativemicrobiology toward being more quantitative
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