1. 1 Historical Perspective on FDA’s Listeria Approach Mickey Parish, Ph.D. Senior Advisor for Microbiology FDA/CFSAN, Office of Food Safety JIFSAN Advisory Board November 6, 2015

2. 2 1996 publication explaining the U.S. position

3. 1996 U.S. position paper: “Public health and regulatory agencies in the USA have established a zero tolerance for Listeria monocytogenes in cooked, ready-to-eat food.” “In 1985 FDA established a policy for L. monocytogenes: detection of the organism in a ready- to-eat food by the FDA method is a violation of the Federal Food, Drug and Cosmetic Act, section 402(a) (1) and (4).” 3

4. 2003 FDA/FSIS Risk Assessment Quantitative assessment of the relative risk for 23 food categories on a per serving basis and a per annum basis. Foodborne listeriosis is relatively rare, but severe. “United States consumers are exposed to low to moderate levels of L. monocytogenes on a regular basis.” Risk of illness depends on the immune status of the individual. Certain foods are more likely to be vehicles for L. monocytogenes 4

5. Prepared at request of Codex Committee on Food Hygiene Intended to provide basis for development of guidelines for control of L. monocytogenes in foods by member countries Ultimately, Codex adopted a policy allowing up to 100 CFU Lm/g in foods that do not support growth of L. monocytogenes, but absence in 25 gram samples for foods that support growth. 5 2004 FAO/WHO Risk Assessment

6. Three specific estimations: (1) risk of serious illness from L. monocytogenes in food when the number of organisms range from absence in 25 g to 1000 colony forming units (CFU) per gram or milliliter, or does not exceed specified levels at the point of consumption. (2) risk of serious illness for consumers in different susceptible population groups (elderly, infants, pregnant women and their fetuses, and immunocompromised patients) relative to the general population; and (3) risk of serious illness in foods that support the growth of L. monocytogenes and in foods that do not support its growth at specific storage and shelf-life conditions 6 2004 FAO/WHO Risk Assessment

7. Key Findings: Nearly all cases of listeriosis result from consumption of high numbers of the pathogen Control measures to reduce contamination frequency will have a proportional reduction in rates of illness Most cases of listeriosis are associated with the consumption of foods that do not meet current standards for L. monocytogenes in foods, whether that standard is zero tolerance or 100 CFU/g. 7 2004 FAO/WHO Risk Assessment

8. FDA 2008 Draft Compliance Policy Guide and Notice of Public Meeting Draft CPG, Guidance for Industry, and Notice of public meeting published Feb 7, 2008 If finalized, CPG would establish policy for Lm in RTE foods based on whether food supports growth or not: –Foods that support growth: Absence of Lm in 25 gram samples of food –Foods that do not support growth: Allowance up to 100 CFU Lm per gram of food 8

9. FDA 2008 Draft Compliance Policy Guide and Notice of Public Meeting Notice of Public Meeting included an estimation of listeriosis cases based on a tabulation of dose-response data from the 2003 risk assessment. Estimation supported the proposed 100/g allowance in foods that do not support growth. 2008 FDA re-tabulation estimated that there would be no annual cases of listeriosis if all servings of RTE foods were at or below 10 5 (100,000) CFU of Lm per serving. 9

10. FDA 2008 Draft Guidance for Industry Intended to encourage industry to focus resources on controlling L. monocytogenes in the production environment for RTE foods Especially important for RTE foods that support growth of L. monocytogenes Also important for RTE foods that do not support growth of L. monocytogenes and for foods not-RTE Included recommendations for sanitation and environmental monitoring. 10

11. FDA 2008 Draft Guidance for Industry Recommends that a food processor that detects the presence of the indicator “Listeria species” on a food- contact surface or in a food to either: –1. Conduct additional testing to determine if the Listeria species is actually L. monocytogenes, or –2. Assume the “Listeria species” positive is due to L. monocytogenes May inhibit firms from testing food-contact surfaces Differs from FSIS approach 11

12. 2013 FDA/FSIS Listeria Risk Assessment for Retail Delis Addressed 1) risk of listeriosis posed by consumption of RTE foods commonly prepared and sold in delicatessens in retail food stores, and 2) how risk may be impacted by changes in practices in the stores. –Prevention of bacterial growth reduced predicted risk of listeriosis –Cross contamination increased predicted risk of listeriosis –Transfer of Lm from incoming product, environment and niches increased predicted risk –Appropriate sanitation practices decreased predicted risk –Slicer is a primary source of cross contamination for deli meats and cheeses 12

13. 2011 JIFSAN-IRAC workshop 2011 JIFSAN/IRAC workshop –(1) Discuss the need to incorporate new data and L. monocytogenes dose-response models in future risk assessments; –(2) Identify novel strategies for L. monocytogenes dose-response modeling, particularly the development of mechanistic microbial dose-response models; and –(3) Identify key factors and data to be considered in future dose- response modeling. Led to refereed publication: Hoelzer et al. 2013. New Data, Strategies, and Insights for Listeria monocytogenes Dose-Response Models: Summary of an Interagency Workshop, 2011. Risk Analysis 33(9): 1568-1599 13

14. 2015 FDA Listeria Dose-Response Model CFSAN published reassessment of dose-response data to adjust for variation in L. monocytogenes strain virulence and host susceptibility for population subgroups. Most listeriosis cases are linked to the ingestion of food contaminated with medium to high concentrations of L. monocytogenes Nonetheless, the model predicts the expected number of cases linked to the consumption of 10,000 cfu or less [100g at 100 CFU/g] in 55 out of 1,591 cases, i.e., 3.5% of cases. 14

15. Noted Illness Events of Recent Years YearImplicated Food Number of Cases Number of Deaths 2010-2015Ice cream103 2014Caramel Apples357 2014Stone fruit10 2014Sprouts52 2013 - 2014Cheese and dairy products51 2013Cheese products81 2013Cheeses61 2012Ricotta salata cheese224 2011Cantaloupe14733 15

16. Reportable Food Registry 156 primary submissions for L. monocytogenes in first four years of RFR Foods most commonly involved are seafood, dairy products, prepared foods, fresh-cut produce, whole produce No clear trends in submissions –Year 1: 33 –Year 2: 40 –Year 3: 48 –Year 4: 35 16

17. Key Question Regarding Lm in Non- growth Foods Question –Is there a low number of Lm that would not result in adverse health consequences for highly vulnerable individuals? Answer –Maybe –However, available data are limited and prevent us from establishing such a number with sufficient certainty to adequately protect public health, esp. for highly vulnerable individuals

18. Key Point Based on various issues such as the 2015 dose- response model and outbreaks of recent years, FDA is concerned that there is greater uncertainty about the 100 CFU/g standard for foods that do not support growth and now questions whether the proposed standard in the 2008 draft CPG provides an appropriate level of protection for the most vulnerable individuals in at-risk subpopulations. 18

19. Key Issues for FAC 19 1. Determining Whether Food is Ready-to-Eat (RTE) 2. Distinguishing RTE Foods on the Basis of Whether the Food Supports the Growth of L. monocytogenes 3. Control of Listeria monocytogenes in RTE Foods 4. Control of Listeria monocytogenes in Produce Packinghouses 5. Priorities for Sampling 6. Recommendations on Dietary Restrictions for the Most Vulnerable Populations

20. Thank You 20