2021-2023 National Advisory Committee on Microbiological Criteria For Foods (NACMCF)

FSIS Charge: Enhancing Salmonella Control in Poultry Products

FSIS is seeking guidance on the overarching risk management question: What types of microbiological criteria (e.g., Salmonella performance standards) might FSIS use to encourage reductions in Salmonella in poultry products so that they are more effective in preventing human Salmonella infections associated with these products?

Kathleen Glass, Chair
Elisabetta Lambertini, Co-chair
Janell Kause
Francisco Zagmutt
Bing Wang
Tanya Roberts
Robert Tauxe
Scott Stillwell
James Dickson
Omar Oyarzabal
Wendy McMahon
Joseph ‘Stan’ Bailey
Haley Oliver
Teshome Yehualaeshet
Randy Worobo
Valentina Trinetta

According to the Centers for Disease Control and Prevention (CDC), Salmonella is responsible for approximately 1.35 million cases of foodborne illness each year in the United States. The U.S. Department of Agriculture (USDA) Food Safety and Inspection Service (FSIS) has established qualitative performance standards to limit the occurrence of Salmonella in poultry products (i.e., carcasses, parts, and comminuted products). The goal of these performance standards is to allow FSIS to verify each regulated establishment’s control for this pathogen in raw products throughout the slaughter process, and, by meeting these standards, achieve national food safety goals. Over the past 25 years, there have been significant reductions in the proportion of poultry contaminated with Salmonella, but no meaningful reduction in human Salmonella infections attributed to poultry products^1,2. Therefore, FSIS is seeking guidance on how to improve the current system for reducing Salmonella in poultry to better protect public health.

In 2019, the National Advisory Committee on Microbiological Criteria for Food (NACMCF) recommended that FSIS move toward risk-based disposition of finished raw poultry product, informed by Salmonella amount and serotype. Since then, several studies suggest that setting microbiological criteria (e.g., performance standards) to limit the amount of Salmonella in products and/or to address serotypes more frequently associated with foodborne illness would better protect public health than the current approach. In addition, several studies have demonstrated the feasibility of developing quantitative microbiological criteria based on a change in the concentration of indicator organisms correlated to Salmonella occurrence. These findings, along with new technologies and advancements in rapid quantification of pathogens in products, present opportunities for FSIS to enhance the microbiological criteria it establishes to measure industry control of Salmonella in poultry products. FSIS seeks input from the NACMCF on the best options for using quantification and/or particular pathogen characteristics, along with a relevant pathogen indicator, to enhance its microbiological criteria and reduce Salmonella illnesses attributed to poultry products consumed in the U.S.

¹Williams, M.S., Ebel, E.D., Saini, G., Nyirabahizi, E. 2020. Changes in Salmonella Contamination in Meat and Poultry Since the Introduction of the Pathogen Reduction; Hazard Analysis and Critical Control Point Rule. Journal of Food Protection 83 (10): 1707–1717.

²Publicly available FSIS sampling verification testing data on Salmonella in chicken analyzed to show percentage decline from 2015−2020 (see: Sampling Results for FSIS Regulated Products | Food Safety and Inspection Service (usda.gov)). Percent change in consumer illnesses attributed to poultry based on the Interagency Food Safety Analytics Collaboration reports from 2012−2020. Tack D.M., Marder E.P., Griffin P.M. et al., 2019. Preliminary Incidence and Trends of Infections with Pathogens Transmitted Commonly Through Food — Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2015–2018. MMWR Morbidity and Mortality Weekly Report 68: 369-373.

Salmonella bacteria are a leading cause of foodborne illness. According to CDC estimates, Salmonella is responsible for approximately 1.35 million illnesses, 26,500 hospitalizations, and 420 deaths every year in the United States. Using weighted outbreak data from 1998–2018, the Interagency Food Safety Analytics Collaboration, a joint effort between CDC, the U.S. Food and Drug Administration, and USDA, estimates that over 20 percent of foodborne salmonellosis is attributed to poultry products.³

FSIS established limits, referred to as performance standards, on the occurrence of Salmonella in poultry products as part of the Pathogen Reduction, Hazard Analysis and Critical Control Point (PR/HACCP) Systems Final Rule. These standards were designed to improve food safety, reducing the risk of foodborne illness, and enable FSIS to verify process control. Process control is a defined procedure or set of procedures designed by an establishment to provide control of those operating conditions that are necessary for the production of safe, wholesome food. The procedures typically include some means of observing or measuring system performance, analyzing the results generated in order to define a set of control criteria, and taking action when necessary to ensure that the system continues to perform within the control criteria. FSIS has since updated those original performance standards. FSIS relies on qualitative (presence/absence) pathogen sampling data to apply performance standards for Salmonella in poultry products. These standards are based on quantitative microbiological risk assessments⁴ and are designed to achieve the national food safety goals. The Healthy People 2020 food safety goal was a 25 percent reduction in foodborne Salmonella illnesses, to achieve fewer than 11.5 Salmonella infections per 100,000 population per year. In 2020, the case rate for Salmonella infection was 13.3 per 100,000 population⁵. FSIS has proposed performance standards for beef products and intends to propose performance standards for pork products.

Since the implementation of Salmonella performance standards for poultry, FSIS has measured a substantively lower occurrence of this pathogen in raw poultry products, but the incidence of human illness associated with consumption of poultry products has not decreased. FSIS is interested in developing microbiological criteria (i.e., an alternative type of performance standard(s)) that will result in a substantively reduced level of human illness from Salmonella in poultry. FSIS is considering microbiological criteria such as the quantity of Salmonella in products, and the presence of Salmonella serotypes more frequently associated with human illness, rather than presence/absence of any Salmonella. Criteria could be set at various points in the food safety system to better assess industry control over Salmonella in these products, for example, prior to establishment interventions and after establishment interventions, to evaluate the effectiveness of an establishment’s food safety system in mitigating Salmonella in products during the slaughter process.

Several recent studies showed a correlation between indicator organisms and Salmonella in poultry. Specifically, a correlation was shown between a change in the quantity of an indicator (i.e., Aerobic Plate Count (APC)) from the carcass to finished product and the occurrence of Salmonella in beef, pork, and poultry⁶. Based on these findings, FSIS is considering developing a quantitative “log-reduction” microbiological criterion (e.g., performance standard) to measure the effectiveness of an establishment’s food safety system in controlling Salmonella in products. FSIS believes this type of performance standard would allow for continued monitoring of industry performance in achieving the Healthy People national food safety goals, thereby improving public health outcomes, while providing better insights on pathogen control throughout the food safety system. As part of this consideration, FSIS would also like to know how the Agency could address Salmonella serotypes more frequently associated with human illness, strain characteristics (e.g., virulence factors), and/or the quantity of Salmonella in a subset of products tested, prior to and after interventions, when evaluating industry’s control of Salmonella.

FSIS is considering the following microbiological criteria to assess industry control:

the presence of any Salmonella or only specific serotypes more likely to cause illness, at preharvest (e.g., as measured at the receiving step in the slaughter process) (see question 1)
the amount of Salmonella and/or presence of serotypes more likely to cause illness, throughout the slaughter process (see questions 2, 3, 5); and
a relevant indicator for Salmonella, throughout the slaughter process (see question 4).

FSIS would like NACMCF to consider these options – or suggest others -- and provide insights to assist FSIS decision making.

³Interagency Food Safety Analytics Collaboration, 2020. Foodborne illness source attribution estimates for 2018 for Salmonella, Escherichia coli O157, Listeria monocytogenes, and Campylobacter using multi-year outbreak surveillance data, United States. Atlanta, Georgia and Washington, District of Columbia: U.S. Department of Health and Human Services, CDC, FDA, USDA/FSIS.
⁴Ebel, E.D., Williams, M.S., Golden, N.J., Marks, H.M., 2012. Simplified framework for predicting changes in public health from performance standards applied in slaughter establishments. Food Control 28, 250-257; Williams, M.S., Ebel, E.D., Vase, D., 2011. Framework for microbiological food-safety risk assessments amenable to Bayesian modeling. Risk Analysis 31, 548-565.
⁵Ray L.C., Collins J.P., Griffin P.M. et al., 2021. Decreased Incidence of Infections Caused by Pathogens Transmitted Commonly Through Food During the COVID-19 Pandemic — Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2017–2020. MMWR Morbidity and Mortality Weekly Report 70: 1332-1336.
⁶Williams M.S., Ebel E.D., Allender H.D. 2015. Industry-level changes in microbiological contamination on market hog and
broiler chicken carcasses between two locations in the slaughter process. Food Control 51: 361-370; Williams M.W., Ebel E.D., Golden N.J. 2017. Using indicator organisms in performance standards for reducing pathogen occurrence in beef carcasses in the United States. Microbiological Risk Analysis 6: 44-56.

FSIS is seeking guidance on the overarching risk management question: What types of microbiological criteria (e.g., Salmonella performance standards) might FSIS use to encourage reductions in Salmonella in poultry products so that they are more effective in preventing human Salmonella infections associated with these products?

Specific risk management questions posed to NACMCF are:

Can we assess the public health impact (e.g., reduction in salmonellosis) of controlling specific Salmonella serotypes and/or amount (levels) in poultry products? What types of approaches could be used?
What types of microbiological criteria could be established to encourage control of Salmonella at preharvest (i.e., in live birds on-farm)?
1. Should FSIS consider qualitative microbiological criteria for control of the presence of Salmonella in a flock when they are presented for slaughter?
2. How could FSIS use these criteria to address Salmonella serotypes most frequently associated with human illness?
3. What industry data would provide evidence of control?
What types of microbiological criteria could be established for poultry carcasses, parts, and comminuted products prior to applying interventions and after interventions, considering current technology?
1. Could the quantity of Salmonella or quantity of microbiological indicator organisms (e.g., APC) be used? What are the key parameters that need to be considered? What data analysis techniques could be used? How would these criteria be linked to human illness?
2. How could serotypes frequently associated with human illness be considered in the development of microbiological criteria?
How might foodborne illness surveillance data on human Salmonella illnesses, data from foodborne outbreaks associated with Salmonella in poultry, and data on Salmonella serotypes in poultry products be used to identify the Salmonella serotypes of greatest public health concern associated with specific poultry products?
1. Should only the most current data (e.g., 5-years) of foodborne illness surveillance, outbreak and/or pathogen testing data be used?
2. Going forward, what methodology and criteria would focus on those Salmonella serotypes most frequently associated with human illness and attributable to poultry products?
3. How frequently should the priority Salmonella serotypes associated with poultry be revised considering changes in their occurrence while still ensuring continuity in industry and regulatory testing?
There is a documented correlation between a reduction in the quantity of APC between carcasses and finished products and the occurrence of Salmonella in finished products for beef, pork, and poultry. How might this information be used to set microbiological criteria to assess process (pathogen) control in poultry?
What rapid methods and technologies are available for the quantification of Salmonella? How should FSIS make the best use of these methods?
Are there particular approaches that would result in selective identification of the serotypes of public health concern?
1. For example, are there approaches to mitigate a potential strain selection bias introduced by the laboratory method?
2. If needed, what type of research could be conducted to ensure performance characteristics of current laboratory methods (e.g., enrichment, incubation, pre-screening) do not result in a biased serotype detection?
How should pathogen characteristics derived from whole genome sequencing (e.g., serotype, virulence, antimicrobial resistance) be considered in the development of microbiological criteria?
What research is needed to support FSIS’ new Salmonella strategy in terms of setting microbiological criteria?

Response to Questions Posed by the Food Safety and Inspection Service: Enhancing Salmonella Control in Poultry Products

FDA Charge: Cyclospora cayetanensis

FDA is seeking information on the factors that can contribute to C. cayetanensis contamination of domestically grown and imported produce, and recommendations for developing an effective prevention and management strategy.

Max Teplitski, Chair
Peggy Cook, Co-chair
Betty Feng
Audrey McMillan-Cole
Joelle Mosso
Mahipal Kunduru
Philip Elliott
De Ann Davis
Joseph Eifert
Francisco Diez-Gonzalez
Patty Lewandowski
Shannara Lynn
Angela Melton-Celsa

Cyclospora cayetanensis is a coccidian protozoan parasite, belonging to the phylum Apicomplexan, order Eucoccidiorida, family Eimeriidae, described between 1993 to 1994 as a newly identified human gastrointestinal pathogen. C. cayetanensis is the only species of the genus Cyclospora known to infect humans. The parasite produces oocysts that are resistant to harsh environmental conditions, as well as resistant to many common chemical treatments to reduce the presence of bacterial pathogens in the produce production environment and in agricultural inputs (e.g. agricultural water). C. cayetanensis is the etiologic agent of the gastrointestinal illness called cyclosporiasis. Detected in association with human illness in many different parts of the world, C. cayetanensis previously was considered to be a pathogen acquired during childhood in developing nations. In the U.S., cyclosporiasis previously was associated with travel outside of the US or consumption of contaminated imported foods. However, in recent years, the U.S. has seen an increase in cases and positive samples associated with produce, both as raw agricultural commodities, and fresh-cut produce, grown in the US. In the last three years, the number of cyclosporiasis cases has increased approximately 300%, often linked to fresh produce consumption, specifically leafy herbs and ready-to-eat salads. Awareness of the factors that can contribute to C. cayetanensis contamination of domestically grown and imported produce, is key to developing an effective prevention and management strategy.

Cyclospora spp. are protozoan parasites in the phylum Apicomplexan that can parasitize different species of mammals with remarkable host-specificity. Cyclospora has a complex life cycle and can only multiply within the infected hosts. Among the Cyclospora species, only Cyclospora cayetanensis is known to infect humans; all other species are associated with infections in other animals. This parasite is characterized by environmentally-hardy oocysts that are shed in stool by the infected persons. These oocysts are shed unsporulated and are not infectious. Once released into the environment, unsporulated oocysts require approximately 7 to 14 days under certain environmental conditions to sporulate and become infectious. The oocysts are thought to be transferred to the surface of foods through environmental routes (e.g., through human fecal pollution carried by agricultural water) subsequently infect the host after produce is consumed. Once consumed, the sporulated oocysts replicate in the human gastrointestinal tract and continue the infection cycle as unsporulated oocysts are shed in stool. The cycle continues as human fecal pollution again contaminates the environment. A limitation to widespread Cyclospora cayetanensis research is the inability to directly culture or propagate the organism. Researchers rely solely on acquired oocysts to conduct research. Some work has been done to use surrogate organisms to mimic the life cycle of Cyclospora cayetanensis, however with limited positive results. A positive C. cayetanensis finding is indicative of the presence of human fecal contamination, as humans are the only known reservoir. Cyclosporiasis is characterized by symptoms such as explosive diarrhea, vomiting, fatigue, and weight loss. C. cayetanensis has become a major public health and food safety concern during the last few years. Outbreaks of cyclosporiasis affect thousands of individuals in the U.S. annually, with a steady increase in reported cases over recent years. In 2020, CDC reported 1,241 laboratory-confirmed cases of cyclosporiasis in people who had no history of international travel. In 2019 and 2018, there were 2,408 and 2,299 cases reported each year, respectively. Comparatively, between 2000–2017, the total number of cases reported for cyclosporiasis in the US was 1,730. Additionally, cyclosporiasis typically results in symptomatic illness in the general population regardless of age in the US, whereas in endemic areas, young children and immunocompromised individuals are most at risk for severe illness. Outbreaks of cyclosporiasis generally occur during the warmer months of May – September for the northern hemisphere, and November – March for the southern hemisphere. Historically, these outbreaks have been linked to ingestion of contaminated berries, fresh cilantro, basil and, more recently, ready-to-eat bagged salads. Several efforts have been implemented to develop molecular detection methods for C. cayetanensis in both food vehicles and environmental water. These methods have been used to assist epidemiological investigations and surveys to estimate the prevalence of C. cayetanensis in commodities and growing regions. Despite these scientific efforts, there are still several significant knowledge and data gaps that hamper the implementation of effective measures to prevent the contamination of produce with the oocysts of this parasite.

What is known about the prevalence, incidence, and burden of disease of cyclosporiasis in the U.S. and internationally?
1. Are there specific segments of the U.S. population that may be at higher risk for infection? What is the geographic distribution of cases in the U.S.?
2. What is the diversity of Cyclospora cayetanensis genotypes in the US and internationally?
3. What factors (e.g., food safety practices, location of the farms) may contribute to contamination with Cyclospora cayetanensis?
4. Are certain factors (e.g., type of food, seasonality, where the food is produced, degree of hand contact during growing and harvesting) more significant than others?
How does the seasonality, incidence and prevalence of cyclosporiasis compare throughout the United States and internationally and what factors may contribute?
1. Extrinsic factors that may influence sporulation and survival (e.g., extrinsic factors influencing sporulation and survival);
2. Environmental factors influencing movement (e.g., rainfall);
3. Other?
What sampling data exists for Cyclospora cayetanensis in food products and environmental samples, domestically and internationally?
1. What trends have been observed?
2. What methods of detection were used?
What types of foods have been attributed to outbreaks of cyclosporiasis domestically and internationally and what (if any) contributing factors, sources or routes of contamination that have been identified?
Is monitoring for Cyclospora cayetanensis by testing food products, agricultural environment and agricultural inputs being applied as a management strategy currently (e.g., by industry, government)?
1. Are there best practices for monitoring for the presence of Cyclospora cayetanensis in agricultural production (including matrices [e.g. water, product], frequency, timing of sample collection (pre vs. post-harvest), and sample numbers)?
2. Has monitoring led to development and implementation of effective preventive measures? If so, how effective have they been?
What are available approaches for characterizing the relatedness of different strains of Cyclospora cayetanensis (e.g., subtyping)?
What are currently available test methods (and comparative sensitivity/specificity) for detecting and/or isolating Cyclospora cayetanensis in different matrices (e.g., food, water, environmental samples)? What type of validation has the method(s) undergone? What are the matrices for which the methods have been validated?
What information exists on assessing viability of oocysts?
What preventive measures exist for the control of Cyclospora cayetanensis (e.g., using filtration)?
1. How effective have they been?
2. What are the impediments to development of effective preventive measures for Cyclospora cayetanensis and how can they be overcome?
What is known about Cyclospora cayetanensis persistence/survival in food, such as produce, and the environment (e.g., soil, water, food contact surfaces)?
What is known about transfer and attachment of Cyclospora cayetanensis from environmental samples (water and soil) to produce?
What other coccidian parasites could serve as a surrogate research model for Cyclospora cayetanensis behavior (e.g., for evaluation of control measures)?
Are there indicator organisms that can be used to determine the likely presence or absence of Cyclospora cayetanensis in various matrices?
What is known about the role of vectors (such as non-human organisms), if any, in the transmission of Cyclospora cayetanensis?
What role do farm workers play in the transfer of Cyclospora cayetanensis contamination during pre-harvest, harvest and post-harvest handling?Are there particular approaches that would result in selective identification of the serotypes of public health concern?
1. How might farm workers serve as both sources and routes of contamination (such as through contamination of agricultural water, or transfer of contaminated soil to food contact surfaces or produce)?
2. What are strategies that have been utilized to mitigate the contamination from farm workers? Have efforts to mitigate contamination from farm workers been successful?
Are there practices for the maintenance and conveyance of wastewater, septage or human waste that may increase the incidence of Cyclospora cayetanensis contamination? Are there practices that may be useful in the management of waste to reduce the potential for contamination by Cyclospora cayetanensis (e.g., third-party toilet service or municipal wastewater treatment)?
1. Which wastewater, septage, and human waste treatments in the U.S. are effective against Cyclospora cayetanensis? Which treatments may not be effective against Cyclospora cayetanensis?
2. Does municipal water treatment adequately reduce, control or eliminate Cyclospora cayetanensis?
3. Can effective municipal water treatments systems be scaled to treat agricultural water used in produce production?
4. How do practices compare for domestic growers versus international growers who export to the U.S.?
What elements or points in the parasite's life cycle are potential targets of strategies to disrupt its progression, eliminate or destroy oocysts, stop dissemination into the environment, and prevent food contamination?
1. What are control measures that should be evaluated for effectiveness against Cyclospora cayetanensis? Including control measures that can be applied to the environment and/or foods that may be consumed in the raw form.
2. What is a recommended protocol for evaluating the effectiveness of control measures against Cyclospora cayetanensis?
What are the relevant factors, available data, and data gaps needed to develop an informative quantitative risk assessment model for Cyclospora cayetanensis contamination and risk of illness?

Subcommittee Report for Cyclospora cayetanensis

FDA Charge: Cronobacter spp. in Powdered Infant Formula

Cronobacter spp. (formerly Enterobacter sakazakii) are microorganisms present in the environment and can survive in dry foods, such as powdered infant formula. Cronobacter spp. infections among infants younger than 12 months have high case-fatality rates. Historical surveys of powdered infant formula have reported a relatively high prevalence rate, ranging from 2 to 15% of Cronobacter spp. contamination in these products. FDA regulations specify that manufacturers of infant formula must establish a system of production and in-process controls, covering all stages of processing, that is designed to ensure that infant formula does not become adulterated due to the presence of Cronobacter spp (see 21 CFR parts 106 and 107). In late 2021 and early 2022, a series of Cronobacter spp. illnesses among infants in the U.S. was associated with feeding powdered infant formula. In each illness, the formula was produced by a specific manufacturer at one facility. The resulting voluntary recall (and the temporary shutdown of the plant) was a major contributing factor to the infant formula shortage experienced across the U.S. in 2022. Better understanding of the factors that contribute to Cronobacter spp. contamination of powdered infant formula and the production environment is needed to increase the effectiveness of prevention and management strategies.

What is the current prevalence and level of Cronobacter spp. contamination in powdered infant formula in the U.S. market? What is known about Cronobacter spp. in other foods and in the home environment and the frequency with which these foods and environmental sources contribute to human infections?
What factors (e.g., virulence factors, host factors, dose of exposure) place an infant at greater risk for Cronobacter spp. infection and serious adverse health consequences or death?
What food safety management practices (e.g., facility and equipment design, hygienic zoning and packaging, preventive controls, verification activities) should manufacturers of powdered infant formula employ to further reduce the risk of Cronobacter spp. contamination of formula and/or the production environment?
Given that powdered infant formula is not sterile, how could food safety messaging be improved for infant care providers, with emphasis on use of sterile, ready-to-use formulas for infants at greatest risk and safe infant formula preparation and storage for infant formula in general?