08-549. Draft Compliance Policy Guide Sec. 555.320 Listeria monocytogenes

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice of meeting.

SUMMARY:

The Food and Drug Administration (FDA) is announcing a public meeting to discuss a Draft Compliance Policy Guide Sec. 555.320 Listeria monocytogenes (the draft CPG) that provides guidance for FDA staff on the agency's enforcement policy for L. monocytogenes in ready-to-eat (RTE) foods that support growth of the organism and RTE foods that do not support growth of the organism.

DATES:

The meeting will be held on March 28, 2008, from 9 a.m. to 4:30 p.m. The closing date for requests to make an oral presentation is March 7, 2008. The closing date for advance registration, for notifying the contact person about a need for special accommodations due to a disability, and for providing a brief description of an oral presentation and any written material for the presentation is March 21, 2008. Persons wishing to park onsite should inform the contact person of their request by March 24, 2008.

ADDRESSES:

The meeting will be held at the Harvey W. Wiley Federal Bldg., Food and Drug Administration, Center for Food Safety and Applied Nutrition, 5100 Paint Branch Pkwy., College Park, MD, 20740-3835 (Metro stop: College Park on the Green Line). Submit electronic registration and requests to make an oral presentation to http://www.cfsan.fda.gov/​register.html. Submit written or oral registration, requests to make an oral presentation, written material for a presentation, and questions in advance of the meeting to the contact person for registration (see FOR FURTHER INFORMATION CONTACT). A transcript of the meeting will be available for review at the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD.

FOR FURTHER INFORMATION CONTACT:

For registration, requests for oral presentation, submission of written material for the presentation, and submission of questions in advance of the meeting: Isabelle Howes, U.S. Department of Agriculture Graduate School, 600 Maryland Ave., SW., suite 270, Washington, DC 20024-2520, 202-314-4713, FAX: [phone], e-mail: [e-mail].

For general questions about the meeting, to request onsite parking, or if you need special accommodations due to a disability: Juanita Yates, Center for Food Safety and Applied Nutrition, Food and Drug Administration, 5100 Paint Branch Pkwy., College Park, MD 20740, 301-436-1731, e-mail: [e-mail].

SUPPLEMENTARY INFORMATION:

I. Registration and Requests for Oral Presentations

Due to limited space and time, we encourage all persons who wish to attend the meeting or to request an opportunity to make an oral presentation to register in advance. We encourage you to register and request an opportunity to make an oral presentation electronically, if possible. You may also register orally or in writing by providing registration information (including name, title, firm name, address, telephone number, fax number, and e-mail address), requests to make an oral presentation, and written material for the presentation to the contact person for registration (see FOR FURTHER INFORMATION CONTACT).

II. Background

FDA has been working with its Federal, State, local, and international food safety counterparts in an effort to reduce the incidence of foodborne illness in the United States, including illness caused by L. monocytogenes. As part of this effort, FDA is announcing elsewhere in this issue of the Federal Register the availability of, and requesting comment on, a draft CPG that provides guidance to FDA staff on the agency's enforcement policy for L. monocytogenes in RTE foods that support growth of the organism and in RTE foods that do not support growth of the organism.

FDA is holding this public meeting to discuss and share information about the enforcement policy in this draft CPG. Stakeholders will have an opportunity to ask questions about the draft CPG and provide oral comments on the draft CPG. Stakeholders may send questions in advance to the contact person identified above (see FOR FURTHER INFORMATION CONTACT). Any questions submitted in advance may be posted without change to http://www.fda.gov/​ohrms/​dockets/​default.htm, including any personal information provided.

III. Transcripts

A transcript of the meeting will be available for review at the Division of Dockets Management (see ADDRESSES) between 9 a.m. and 4 p.m. Monday through Friday and on the Internet at http://www.fda.gov/​ohrms/​dockets/​default.htm, approximately 30 days after the hearing. Written transcripts of the meeting may be requested in writing from the Freedom of Information Office (HFI-35), Food and Drug Administration, 5600 Fishers Lane, rm. 6-30, Rockville, MD 20857, approximately 15 working days after the meeting at a cost of 10 cents per page.

IV. Background and Rationale for the Establishment of the Enforcement Policy

A. Introduction

This document presents the background and rationale for the establishment of an enforcement policy for L. monocytogenes in RTE foods based on whether the food does, or does not, support its growth. Under section 402(a)(1) of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 342(a)(1)), a food shall be deemed to be adulterated if it bears or contains any poisonous or deleterious substance which may render it injurious to health, except that if the substance is not an added substance such food shall not be considered adulterated if the quantity of such substance in such food does not ordinarily render it injurious to health. Courts have interpreted the phrase “injurious to health” as encompassing protection of the health of vulnerable subpopulations. See United States of America v. Lexington Mill & Elevator Co., 232 U.S. 399, 411 (1914).¹ L. monocytogenes is an added deleterious substance in food. United States of America v. Union Cheese Co., 902 F. Supp. 778, 786 (N.D. Ohio 1995).

We are issuing for public comment a draft CPG that, when finalized, would provide guidance for FDA staff as follows:

• For RTE foods that support the growth of L. monocytogenes, FDA may regard the food as adulterated within the meaning of section 402(a)(1) of the Act (21 U.S.C. 342(a)(1)) when L. monocytogenes is present in the food, based on an analytical method that can detect 1.0 colony forming units (cfu) of L. monocytogenes per 25 grams (g) of food (i.e., 0.04 cfu/g).
• For RTE foods that do not support the growth of L. monocytogenes, FDA may regard the food as adulterated within the meaning of section 402(a)(1) of the act (21 U.S.C. 342(a)(1)) when L. monocytogenes is present at or above 100 cfu/g of food.

B. Background on L. monocytogenes

L. monocytogenes is a pathogenic bacterium. Foods that are contaminated with L. monocytogenes and consumed without thorough cooking have been associated with a mild non-invasive illness with flu-like symptoms (called listerial gastroenteritis) and a rare but potential severe disease (called listeriosis). Listeriosis predominately affects fetuses and neonates who are infected after the mother is exposed to L. monocytogenes during pregnancy, the elderly, and persons with weakened immune systems. Listeriosis is characterized by a high case-fatality rate, ranging from 20 percent to 30 percent. Most cases of human listeriosis occur sporadically—that is, in an isolated manner without any apparent pattern. However, much of what is known about the epidemiology of the disease has been derived from outbreak-associated cases, in which there is an abrupt increase in reports of the disease. Foods that have been implicated in sporadic cases or outbreaks of listeriosis have been foods (including coleslaw, fresh soft cheese made with unpasteurized milk, frankfurters,² deli meats, and butter) that are RTE. (Ref. 1).

L. monocytogenes is widespread in the environment. It is found in soil, water, sewage, and decaying vegetation. It has been isolated from humans, domestic animals, raw agricultural commodities, and food processing environments (particularly cool damp areas) (Refs. 2 through 4). Control of L. monocytogenes in the food processing environment has been the subject of a number of scientific publications (Refs. 5 through 7). L. monocytogenes can survive longer under adverse environmental conditions than many other vegetative bacteria that present a food safety concern. L. monocytogenes tolerates high salt concentrations (such as in nonchlorinated brine chiller solutions) and survives frozen storage for extended periods. It is more resistant to nitrite and acidity than many other foodborne pathogens. It also is more resistant to heat than many other nonspore forming foodborne pathogens, although it can be killed by heating procedures such as those used to pasteurize milk³ (Ref. 8). Importantly, L. monocytogenes can multiply slowly at refrigeration temperatures, thereby challenging an important defense against foodborne pathogens—i.e., refrigeration (Refs. 9 and 10).

Some foods (such as ice cream and pickled fish) are characterized by intrinsic or extrinsic factors⁴ that generally prevent the growth of L. monocytogenes (i.e., they are “listeristatic”), or are processed to alter the normal characteristics of the food. For example, it is well established (Refs. 10 and 12 through 14) that L. monocytogenes does not grow when:

• The pH of the food is less than or equal to 4.4;
• The water activity of the food is less than or equal to 0.92; or
• The food is frozen.

Foods may naturally have a pH or water activity that prevents growth of L. monocytogenes or may be deliberately processed to achieve those characteristics (e.g., by adding acid to deli-type salads to bring the pH to less than or equal to 4.4). Listeristatic control measures, such as some antimicrobial substances, can prevent L. monocytogenes from growing in food (Ref. 10).⁵

Examples of RTE foods that generally are considered to not support the growth of L. monocytogenes include:⁶

• Fish that are preserved by techniques such as drying, pickling, and marinating;
• Ice cream and other frozen dairy products;
• Processed cheese (e.g., cheese foods, spreads, slices);
• Cultured milk products (e.g., yogurt, sour cream, buttermilk);
• Hard cheeses (less than 39 percent moisture) (e.g., cheddar, colby, and parmesan);
• Some deli-type salads, particularly those processed to a pH less than 4.4 and those containing antimicrobial substances such as sorbic acid/sorbates or benzoic acid/benzoates under conditions of use documented to be effective in preventing the growth of L. monocytogenes;
• Some vegetables (such as carrots); and
• Crackers, dry breakfast cereals, and other dry foods that have water activity less than 0.92 (Ref. 10).

In contrast, other foods (such as milk and crabmeat) do not have factors that prevent the growth of L. monocytogenes. These foods support the growth of L. monocytogenes. Examples of RTE foods that support the growth of L. monocytogenes include:

• Milk;
• High fat and other dairy products (e.g., butter and cream);
• Soft unripened cheeses (greater than 50 percent moisture) (e.g., cottage cheese and ricotta cheese);
• Cooked crustaceans (e.g., shrimp and crab);
• Smoked seafood (e.g., smoked finfish and mollusks);
• Raw seafood that will be consumed as sushi or sashimi;
• Many vegetables (such as broccoli, cabbage and salad greens);
• Non-acidic fruit (such as melon, watermelon, and papaya) (Ref. 17; and
• Some deli-type salads and sandwiches (particularly those containing seafood and those prepared at retail establishments without the addition of antimicrobial substances).

Appendix 8 of Reference 1 lists some of the available information on the growth of L. monocytogenes in specific foods, such as several categories of cheese, that include some products that support growth as well as other products that do not support growth. Although Appendix 8 of Reference 1 has very limited information about the growth of L. monocytogenes in fruits, Table 3.3 in Reference 10 reports the pH of many fruits. Table 3.3 in Reference 10 also reports the pH of many vegetables. For example, Table 3.3 in Reference 10 reports that the pH of honeydew melons is 6.3-6.7, the pH of limes is 1.8-2.0, the pH of corn is 7.3, and the pH of cucumbers is 3.8.

C. FDA Activities Addressing L. monocytogenes in RTE Food

Beginning in 1980, a number of reports linked listeriosis outbreaks with various RTE foods, including coleslaw (Ref. 18), pasteurized milk (Ref. 19), and Mexican-style soft, white cheese (Ref. 20). In 1986, FDA revised Compliance Policy Guide (CPG) Sec. 527.300 Pathogens in Dairy Products (7106.08) to address L. monocytogenes (Ref. 21). CPG Sec. 527.300 provides guidance for initiating legal action in cases involving dairy products found to be improperly pasteurized, contaminated with pathogenic microorganisms, or prepared and packed under insanitary conditions. One criterion for initiating legal action is that analysis of the dairy product demonstrates that one or more units is positive for L. monocytogenes and is confirmed. The specimen charge recommended by CPG Sec. 527.300 when this criterion is met is that the article is adulterated within the meaning of 21 U.S.C. 342(a)(1) in that it contains a pathogenic microorganism, namely L. monocytogenes, which may render it injurious to health. See United States of America v. Union Cheese Co., 902 F. Supp. 778, 786 (N.D. Ohio 1995) (holding that the “presence of L. monocytogenes” rendered defendant's cheese products adulterated within the meaning of 21 U.S.C. 342(a)(1)). Consistent with the guidance in CPG Sec. 527.300 and with the Union Cheese decision, we issued warning letters or sought injunction when we detected L. monocytogenes in foods other than dairy products, such as cut salad or smoked seafood (Ref. 22 and United States of America v. Blue Ribbon Smoked Fish, Inc., 179 F. Supp. 2d 30 (E.D.N.Y. 2001)).⁷

A 1996 paper authored by FDA staff and entitled “U.S. position on Listeria monocytogenes in foods” (Ref. 23) stated that, based on the available scientific information, FDA considered detection of L. monocytogenes in cooked, RTE foods to be a violation of section 402(a)(1) of the act, in that the food bears or contains an added poisonous or deleterious substance which may render it injurious to health. The authors stated that FDA had established a “zero tolerance” for L. monocytogenes in cooked, RTE foods. The authors used the term “zero tolerance” to indicate that FDA considered any detectable level of L. monocytogenes in cooked, RTE foods to be unacceptable from a public health perspective.

FDA uses an analytical method that can detect 1.0 cfu of L. monocytogenes per 25 g of food to determine whether L. monocytogenes is present in the food (i.e., 0.04 cfu/g) (Ref. 24).

D. Microbiological Limits Established Internationally for L. monocytogenes

Some international entities are approaching the contamination of foods with L. monocytogenes with different microbiological limits for the food depending on whether the food does, or does not, support the growth of L. monocytogenes. For example, Canada has adopted a three-tiered enforcement policy for foods that may be contaminated with L. monocytogenes (Ref. 25). The first tier addresses L. monocytogenes in RTE foods that have been associated with an outbreak of listeriosis or that were placed in the “high risk” category in a 2003 quantitative risk assessment released by FDA and FSIS (Ref. 1). For foods in the first tier, the presence of L. monocytogenes in the food is a Health 1 concern⁸ unless the measured pH or water activity, or data provided by the manufacturer, demonstrates that the product does not support the growth of L. monocytogenes. The second tier addresses L. monocytogenes in RTE foods that are capable of supporting the growth of L. monocytogenes and have a shelf life exceeding 10 days. For foods in the second tier, the presence of L. monocytogenes in the food is a Health 2 concern unless data provided by the manufacturer demonstrate that the product does not support the growth. The third tier addresses RTE products that: (1) Support growth of L. monocytogenes, but have a shelf life of equal to or less than 10 days, or (2) do not support growth of L. monocytogenes. Foods in the third tier have the lowest priority, in terms of inspection and compliance action, unless the product is produced for, or targeted or distributed to, sensitive populations (such as pregnant women or immunocompromised individuals). For foods in the third tier, product containing greater than 100 cfu/g of L. monocytogenes is a Health 2 concern, except that the presence of L. monocytogenes in product that is produced for, or targeted or distributed to, sensitive populations is considered a Health 1 or Health 2 concern, based on consideration of all available information.

As another example, the Commission of the European Community has established a directive that establishes a series of food safety criteria for L. monocytogenes depending on the intended use of the food and depending on whether the food remains under the control of the food business operator or is in the market (Ref. 27). For example, the food safety criterion for RTE foods intended for infants or for special medical purposes is the presence of L. monocytogenes in the food, regardless of whether the food supports its growth. The food safety criterion for RTE foods that do not support the growth of L. monocytogenes is 100 cfu/g. The food safety criterion for RTE foods (other than those intended for infants or for special medical purposes) that support the growth of L. monocytogenes is the presence of detectable L. monocytogenes in the food before the food has left the immediate control of the food business operator, or 100 cfu/g after the food is in the market.

E. Establishing an Enforcement Policy for L. monocytogenes in RTE Foods

In 2001, FDA and USDA/FSIS, in consultation with the Centers for Disease Control and Prevention of the United States Department of Health and Human Services, requested comment on a draft quantitative assessment (the 2001 Draft LmRA) (Ref. 28) of relative risk associated with consumption of 20 categories of RTE foods that had a history of contamination with L. monocytogenes, or that were implicated epidemiologically with an outbreak or a sporadic case of listeriosis. In 2003, FDA and USDA released their final risk assessment (the FDA/FSIS LmRA) (Ref. 1), which includes revisions made after review of comments received to the 2001 Draft LmRA. The FDA/FSIS LmRA (Ref. 1) provides the scientific basis for the enforcement policy that is the subject of the draft CPG.

In 2004, the Food and Agriculture Organization (FAO) and the World Health Organization (WHO) of the United Nations (FAO/WHO) issued a Risk Assessment of Listeria monocytogenes in Ready-to-Eat Foods (the FAO/WHO LmRA) (Ref. 29). This risk assessment, prepared at the request of the Codex Committee on Food Hygiene (CCFH) was intended to provide a scientific basis for the development of guidelines for the control of L. monocytogenes in foods by member countries. Representatives of FDA participated in development of this FAO/WHO Risk Assessment, which relied on data and information in the 2001 Draft FDA/FSIS LmRA. The FAO/WHO LmRA provides additional scientific information that supports the enforcement policy that is the subject of the draft CPG.

Both the FDA/FSIS LmRA and the FAO/WHO LmRA are quantitative risk assessments that use mathematical modeling to estimate risk and assume that individuals in a population may have varying susceptibility to infection. The dose-response models developed in these risk assessments are nonthreshold models that assume that a single cell has the potential to infect and provoke a response in an individual (Ref. 30). As a result, under these models the risk presented by foodborne L. monocytogenes does not reach zero unless the number of L. monocytogenes in a food serving is zero. Another consequence of the nonthreshold model is that an increase in either the frequency of contamination (percentage of food servings that are contaminated) or the level of contamination (cfu/g in a contaminated food serving) is expected to result in an increase in the risk of listeriosis (see p. 138 of Part 5 of the FAO/WHO LmRA). Conversely, a decrease in either the frequency of contamination or the level of contamination is expected to result in a decrease in the risk of listeriosis.

The FDA/FSIS LmRA and the FAO/WHO LmRA differ in aspects such as focus (i.e., the questions that the risk assessments addressed), modeling assumptions, source of data regarding exposure, and estimation of serving size. For example, the FAO/WHO LmRA relies on the exposure data in the 2001 Draft LmRA, whereas the FDA/FSIS LmRA relies on revised exposure data that reflect modified food categories, contamination data, growth data, and data on how long foods are stored before consumption. As another example, the FDA/FSIS LmRA used empirical distributions derived from consumer surveys to describe the serving sizes in the food categories. These distributions were expressed as a series of population percentiles of the amount of food eaten per serving, weighted to reflect the consumption survey demographics. In contrast, the FAO/WHO LmRA assumed a uniform serving size of 31.6 g because this serving size both approximated a typical serving size and simplified the calculations in that dose levels were estimated in 0.5 log₁₀ increments.

The FDA/FSIS LmRA and the FAO/WHO LmRA also differ in reported output. For example, the FDA/FSIS LmRA provides information grouping its results as a two-dimensional matrix with five overall risk designations (very high, high, moderate, low, and very low) (see Figure VII-1 in Section VII of the FDA/FSIS LmRA, p. 230), whereas the FAO/WHO LmRA provides tables that report the annual incidence of listeriosis estimated to be associated with specific ingested doses of L. monocytogenes (see, e.g., Table 2.19 in Part 2, p. 58 and Table 5.3 in Part 5, p. 137).

FAO/WHO characterize their dose-response model as a conservative model that assumes maximum virulence of L. monocytogenes (see discussions in Parts 2 and 5 of the FAO/WHO LmRA). One factor that FAO/WHO identify as relevant to this characterization is their assumption that the maximum dose to which L. monocytogenes could grow in a food is 10^7.5 cfu/serving.⁹ In contrast, the dose-response model in the FDA/FSIS LmRA assumed a distribution of virulent strains and that the maximum dose to which L. monocytogenes could grow in a food is 10¹⁰ cfu/serving. The FAO/WHO LmRA includes a table (Table 2.19, see Part 2, p. 58 of the FAO/WHO LmRA) that shows the impact of these different assumptions about the maximum dose to which L. monocytogenes could grow in a food on their estimate of the annual number of illnesses in the susceptible population. Their least conservative assumption about the maximum dose to which L. monocytogenes could grow in a food (i.e., 10^10.5 cfu/serving) is similar to the assumption used in the FDA/FSIS LmRA (i.e., 10¹⁰ cfu/serving).

Applying the exposure assessment and the dose response model in the FDA/FSIS LmRA, we estimate that there would be no annual cases of listeriosis in the total population if all servings of RTE foods were at or below 10⁵ cfu/serving (corresponding to 10³ cfu/g or less for a 100 g serving of food)¹⁰ (see Table 5 in Appendix 1 of this document). We also estimate that the median number of cases of listeriosis would be approximately 1 per year in the total population from all the servings that are contaminated with 10⁷ cfu/serving or less (corresponding to 10⁵ cfu/g or less for a 100 g serving of food) and approximately 6 per year in the total population from all the servings that are contaminated with up to and including 10⁸ cfu/serving (corresponding to 10⁶ cfu/g for a 100 g serving of food). Above doses of 10⁸ cfu/serving, the estimated median number of cases of listeriosis in the total population per year increases exponentially.

These estimates are in line with the estimates reported by FAO/WHO using their least conservative assumption regarding the maximum dose to which L. monocytogenes could grow in a food (see Table 2.19 in Part 2, p. 58 of the FAO/WHO LmRA). As can be seen from FAO/WHO Table 2.19, FAO/WHO estimate that there would be no annual cases of listeriosis in the susceptible population¹¹ if all servings of RTE foods were at or below 10^4.5 cfu/serving (corresponding to 10³ cfu/g or less for a 31.6 g serving of food). FAO/WHO also estimate that the number of cases of listeriosis would be approximately 1 per year in the susceptible population from all the servings that are contaminated with 10^5.5 cfu/serving or less (corresponding to 10⁴ cfu/g or less for a 31.6 g serving of food) and approximately 6 per year in the susceptible population from all the servings that are contaminated with up to and including 10^6.5 cfu/serving (corresponding to 10⁵ cfu/g for a 31.6 g serving of food). When the most conservative modeling assumptions are used, FAO/WHO estimate that there would be no annual cases of listeriosis in the susceptible population if all servings of RTE foods were at or below 10^1.5 cfu/serving (corresponding to 1 cfu/g or less for a 31.6 g serving of food), that the number of cases of listeriosis would be approximately 1 per year in the susceptible population from all the servings that are contaminated with 10^2.5 cfu/serving or less (corresponding to 10 cfu/g or less for a 31.6 g serving of food), and that the number of cases of listeriosis would be approximately 2 per year in the susceptible population from all the servings that are contaminated with up to and including 10^3.5 cfu/serving (corresponding to 10² cfu/g for a 31.6 g serving of food).

The FDA/FSIS LmRA and other scientific information cited in that document support a conclusion that RTE foods that support the growth of L. monocytogenes are much more likely than other foods to be associated with listeriosis. In the United States and other countries, both outbreaks and sporadic cases of listeriosis have been overwhelmingly associated with foods that support the growth of L. monocytogenes. The FDA/FSIS LmRA estimates that only a small percent of contaminated servings would be highly contaminated (see Table III-17 in Section III, p. 75). We estimate that it is these higher dose exposures that are responsible for most of the reported illnesses (See Table 5 in Appendix 1 of this document).

In contrast, the FDA/FSIS LmRA and other scientific information cited in that document support a conclusion that RTE foods that do not support the growth of L. monocytogenes present a low or very low risk (as those terms are defined in the risk assessment) of listeriosis.¹² The FDA/FSIS LmRA estimates that foods that do not support the growth of L. monocytogenes are associated, in total, with less than one case per billion servings and less than one case per year (see Table V-6 in Section V, p. 133 of the FDA/FSIS LmRA).

Because the difference in risk of listeriosis is linked to the ability of a RTE food to support the growth of L. monocytogenes, it is appropriate under a risk-based approach to regard RTE foods differently based on whether the food does, or does not, support the growth of L. monocytogenes.

Since RTE foods that do not support the growth can be expected to have the same level of L. monocytogenes at the point of consumption that they contain at the point when they leave the manufacturer, the appropriate public health strategy is to establish an enforcement policy that is based on the risk presented by consumption of various doses of L. monocytogenes in these foods. The numerical value of the microbiological limit used in a number of other countries for RTE foods that do not support the growth of L. monocytogenes, and the numerical value supported by the FDA/FSIS LmRA, is 100 cfu/g. FDA believes that an enforcement policy aimed at maintaining L. monocytogenes below 100 cfu/g for such foods is protective of most vulnerable populations, since these populations are included in the total population considered in the FDA/FSIS LmRA and the susceptible population considered in the FAO/WHO LmRA.¹³ Methods to enumerate L. monocytogenes are available.¹⁴

In contrast, a RTE food that supports the growth of L. monocytogenes may pose a risk to public health if it contains any detectable L. monocytogenes, because the cfu/serving can reasonably be expected to increase to a dose that is injurious to health during storage periods after manufacture. Low levels after manufacture may become high levels at the time of consumption. Therefore, the appropriate public health strategy for RTE foods that support the growth of L. monocytogenes is to regard the food as adulterated if L. monocytogenes is present in the food. As noted above (see sections IV.A and IV.C of this document), FDA uses an analytical method that can detect 1.0 cfu of L. monocytogenes per 25 g of food (i.e., 0.04 cfu/g) (Ref. 24).

The FDA/FSIS LmRA estimates that it would be rare to find L. monocytogenes at greater than 100 cfu/g in RTE foods that do not support its growth (see Table III-16 in the FDA/FSIS LmRA and Appendix 2 of this document). Thus, we expect that maintaining contamination below 100 cfu/g is achievable for RTE foods that do not support the growth of L. monocytogenes.

FDA anticipates that the public health benefits of this enforcement policy include clarifying for FDA staff which foods support growth of L. monocytogenes and, thus, helping to ensure that FDA resources are focused on foods that are more likely to pose a greater risk to public health. FDA anticipates that it may be able to increase the number of samples that it periodically collects and tests for RTE foods that do not support the growth of L. monocytogenes while it continues to focus its inspection and outreach efforts on facilities manufacturing RTE foods that support the growth of L. monocytogenes. States and local governments could adopt this model for resource allocation. The policy may also indirectly lead to other public health benefits, such as verification strategies and reformulation of some RTE foods (e.g., through addition of antimicrobials, manipulation of pH, or other means) so that they do not support the growth of L. monocytogenes.

V. References

We have placed the following references on display in the Division of Dockets Management (see ADDRESSES). You may see them between 9 a.m. and 4 p.m., Monday through Friday. FDA has verified the Web site addresses, but FDA is not responsible for any subsequent changes to Web sites after this document publishes in the Federal Register.

1. U.S. Food and Drug Administration and U.S. Food Safety and Inspection Service, “Quantitative Assessment of the Relative Risk to Public Health from Foodborne Listeria monocytogenes Among Selected Categories of Ready-to-Eat Foods,” 2003. Available in Docket No. 1999N-1168, vols. 23 through 28, and at http://www.foodsafety.gov/​~dms/​lmr2-toc.html. Cited page numbers refer to the Portable Document File (PDF) version of the document on the Web.

2. National Advisory Committee on Microbiological Criteria for Foods (NACMCF), “Listeria monocytogenes: Recommendations by the National Advisory Committee on Microbiological Criteria for Foods,” International Journal of Food Microbiology, vol. 14, pp. 185-246, 1991. Available in Docket No. 1999N-1168, vol. 0015 bkg1 (12 of 17), Tab 287.

3. Fenlon, D. R., J. Wilson, and W. Donachie, “The Incidence and Level of Listeria monocytogenes Contamination of Food Sources at Primary Production and Initial Processing,” Journal of Applied Bacteriology, vol. 81, pp. 641-650, 1996. Available in Docket No. 1999N-1168, vol. 0011 bkg1 (08 of 17), Tab 134.

4. Fenlon, D. R., “Listeria monocytogenes in the Natural Environment,” Listeria, Listeriosis, and Food Safety, 2d ed., pp. 21-37 (E. T. Ryser and E. H. Marth, editors), Food Science and Technology, New York, Marcel Dekker, Inc., 1999. Available in Docket No. 1999N-1168, vol. 0009 bkg1 (06 of 17), file name bkg0001_5_a.pdf.

5. Tompkin, R. B., “Control of Listeria monocytogenes in the Food Processing Environment,” Journal of Food Protection, vol. 65, pp. 709-725, 2002.

6. Moretro, T. and S. Lansgrund, “Listeria monocytogenes: Biofilm Formation and Persistence in Food Processing Environments,” Biofilms, vol. 1, pp. 107-121, 2004.

7. Gall, K., V. N. Scott, R. Collette, et al., “Implementing Targeted Good Manufacturing Practices and Sanitation Procedures to Minimize Listeria Contamination of Smoked Seafood Products,” Food Protection Trends, vol. 24, No. 5, pp. 302-315, 2004.

8. Doyle, M. E., A. S. Mazzotta, T. Wang, et al., “Heat Resistance of Listeria monocytogenes,” Journal of Food Protection, vol. 64, No. 3, pp. 410-429, 2001.

9. Lou, Y. and A. E. Yousef, “Characteristics of Listeria monocytogenes Important to Food Processors,” Listeria, Listeriosis, and Food Safety, 2d ed., pp. 131-224 (E. T. Ryser and E. H. Marth, editors), Food Science and Technology, New York, Marcel Dekker, Inc., 1999. Available in Docket No. 1999N-1168, vol. 0014 bkg1 (11 of 17), Tab 245.

10. Institute of Food Technologists, IFT/FDA Contract No. 223-98-2333, “Evaluation and Definition of Potentially Hazardous Foods,” 2001. Available at http://www.cfsan.fda.gov/​~comm/​ift4-toc.html. Accessed and printed on April 6, 2007.

11. Russell, N. J. and G. W. Gould, “Major Preservation Technologies,” Food Preservatives, 2d ed., p. 15 (N. J. Russell and G. W. Gould, editors), Springer Publishing Co., New York, 2003.

12. Sorrells, K. M., D. C. Enigl, and J. R. Hatfield, “Effect of pH, Acidulant, Time, and Temperature on the Growth and Survival of Listeria monocytogenes,” Journal of Food Protection, vol. 52, No. 8, pp. 571-573, 1989.

13. Petran, R. L. and E. A. Zottola, “A Study of Factors Affecting Growth and Recovery of Listeria monocytogenes Scott A,” Journal of Food Science, vol. 54, No. 2, pp. 458-460, 1989.

14. Tienungoon, S., D. A. Ratkowsky, T. A. McMeekin, et al., “Growth Limits of Listeria monocytogenes as a Function of Temperature, pH, NaCl, and Lactic Acid,” Applied and Environmental Microbiology, vol. 66, No. 11, pp. 4979-4987, 2000.

15. Leistner, L., “Principles and Applications of Hurdle Technology,” New Methods of Food Preservation (G. W. Gould, editor), London: Blackie Academic & Professional, pp. 1-21, 1995.

16. Scott, V. N., K. M. J. Swanson, T. A. Freier, et al., “Guidelines for Conducting Listeria monocytogenes Challenge Testing of Foods,” Food Protection Trends, vol. 25, No. 11, pp. 818-825, 2005.

17. Penteado, A. L. and M. F. F. Leitao, “Growth of Listeria monocytogenes in Melon, Watermelon and Papaya Pulps,” International Journal of Food Microbiology, vol. 92, pp. 89-94, 2004.

18. Schlech, W. F., III, P. M. Lavigne, R. A. Bortolussi, et al., “Epidemic Listeriosis: Evidence for Transmission by Food,” Medical Intelligence, vol. 308, pp. 203-206, 1983. Available in Docket No. 1999N-1168, vol. 0018 bkg1 (15 of 17), Tab 363.

19. Fleming, D. W., S. L. Cochi, K. L. MacDonald, et al., “Pasteurized Milk as a Vehicle of Infection in an Outbreak of Listeriosis,” New England Journal of Medicine, vol. 312, pp. 404-407, 1985. Available in Docket No. 1999N-1168, vol. 0011 bkg1 (08 of 17), Tab 139.

20. Linnan, M. J., L. Mascola, X. D. Lou, et al., “Epidemic Listeriosis Associated with Mexican-Style Cheese,” New England Journal of Medicine, vol. 3, No. 19, pp. 823-828, 1988. Available in Docket No. 1999N-1168, vol. 0014 bkg1 (11 of 17), Tab 241.

21. Compliance Policy Guide Sec. 527.300 Pathogens in Dairy Products (CPG 7106.08). Accessed and printed on April 8, 2007. FDA makes the most recent edition of the CPG available at http://www.fda.gov/​ora/​compliance_​ref/​cpg/​cpgfod/​cpg527-300.html. When a CPG is revised, previous editions are no longer available on the Internet.

22. Letter from J. H. Rahto of FDA, Minneapolis District Office to Bradley V. Beckman, Custom Cuts Co., March 5, 1999. Available at http://www.fda.gov/​foi/​warning_​letters/​archive/​m2438n.pdf. Accessed and printed on September 30, 2005.

23. Shank, F. R., E. L. Elliot, K. Wachsmuth, et al., “U.S. Position on Listeria monocytogenes in Foods,” Food Control, vol. 7, No. 415, pp. 229-234, 1996. Available in Docket No. 1999N-1168, vol. 0018 bkg1 (15 of 17), Tab 374.

24. U.S. Food and Drug Administration, Bacteriological Analytical Manual Online, Chapter 10—“Listeria monocytogenes,” “Detection and Enumeration of Listeria monocytogenes in Foods,” 2003. Available at http://www.cfsan.fda.gov/​~ebam/​bam-10.html. Accessed and printed on April 10, 2007.

25. Health Canada, “Policy on Ready-to-Eat Foods Contaminated with Listeria monocytogenes,” 2004. Available at http://www.hc-sc.gc.ca/​fn-an/​alt_​formats/​hpfb-dgpsa/​pdf/​legislation/​policy_​listeria_​monocytogenes_​politique_​toc_​e.pdf. Accessed and printed on April 6, 2007.

26. Health Canada, “Health Products and Food Branch (HPFB) Standards and Guidelines for Microbiological Safety of Food—An Interpretive Summary,” 2006. Available at http://www.hc-sc.gc.ca/​fn-an/​res-rech/​analy-meth/​microbio/​volume1/​intsum-somexp_​e.html. Accessed and printed on October 11, 2007.

27. Commission of the European Communities, “Commission Regulation (EC) No 2073/2005 of 15 November 2005 on Microbiological Criteria for Foodstuffs,” Official Journal of the European Union, 22.12.2005 L338/1-L338-26, 2005. Available at http://europa.eu.int/​eur-lex/​lex/​LexUriServ/​site/​en/​oj/​2005/​l_​338/​l_​33820051222en00010026.pdf. Accessed and printed on May 10, 2007.

28. U.S. Food and Drug Administration and U.S. Food Safety and Inspection Service, “Draft Assessment of the Relative Risk to Public Health from Foodborne Listeria monocytogenes Among Selected Categories of Ready-to-Eat Foods,” 2001. Available at http://www.foodsafety.gov/​~dms/​lmrisk.html. Accessed and printed on April 10, 2007.

29. Food and Agriculture Organization and World Health Organization, “Risk Assessment of Listeria monocytogenes in Ready-to-Eat Foods,” Microbiological Risk Assessment Series No. 5. Technical Report, 2004. Available at http://www.who.int/​foodsafety/​publications/​micro/​mra_​listeria/​en/​index.html. Accessed and printed on May 10, 2007.

30. Haas, C. N., “Estimation of Risk Due to Low Doses of Microorganisms: A Comparison of Alternative Methodologies,” American Journal of Epidemiology, vol. 118, No. 4, pp. 573-582, 1983.

Appendix 1.—Data Output and Calculations Relevant to the Annual Incidence of Listeriosis Estimated in The FDA/FSIS LMRA

Table IV-12 of the FDA/FSIS LmRA (Section IV, p. 110) reports the relationship between the dose of L. monocytogenes (in cfu/serving) and the response (as the estimated median mortality rate per serving) for each of three age-based national population groups. The three population groups are the elderly population (60 years and older), perinatal population (prenatal and neonatal), and the remaining population (designated the intermediate-aged).

We took the output data of the model used in the FDA/FSIS LmRA and re-tabulated the data to show our estimates of the annual number of cases of listeriosis in the elderly population, the intermediate-age population, and the neonatal population, as well as in the total population, as a function of the ingested dose (in colony forming units, i.e., cfu) per serving. Tables 1 through 4 report that output data.

Table 1 reports the estimated ascending cumulative percentage of contaminated food servings consumed annually by the elderly population at a series of doses (in cfu/serving) and the estimated ascending cumulative percentage of illnesses in the elderly population. The data are reported at the 5th, 50th (median), and 95th percentiles. Tables 2 through 4 report these data for the intermediate-age, neonatal, and total populations, respectively.

Table IV-11 of the FDA/FSIS LmRA (Section IV, p. 105) reports the estimated total number of illnesses for each population on an annual basis as follows:

• Elderly population: 1159
• Intermediate-age population: 702
• Neonatal population: 216
• Total population: 2078

For each population, we calculated the incremental increase in the estimated percentage of contaminated servings and the incremental increase in the estimated percentage of illnesses. We then multiplied the estimated incremental percentage of illnesses by the estimated total number of illnesses for that population to obtain an estimate of the number of listeriosis cases per year for each dose. Table 5 reports the 50th percentile (i.e., median) calculated estimates of the annual number of cases of listeriosis in the elderly population, the intermediate-age population, and the neonatal population, as well as in the total population, as a function of the ingested dose per serving (i.e., cfu/serving). Table 5 also shows the calculated level (in cfu/g) corresponding to a 100 g serving size.

Table 1.—Output from the Model in the FDA/FSIS LmRA Elderly Population

Dose (cfu/serving)	Estimated Servings (Cumulative Percentage)a	Estimated Illnesses (Cumulative Percentage)b
0	97.91% (92.85%, 98.72%)	0.00% (0.00%, < 0.01%)
1 x 10-4	97.92% (92.85%, 98.72%)	0.00% (0.00%, < 0.01%)
3.16 x 10-4	97.92% (92.86%, 98.73%)	0.00% (0.00%, < 0.01%)
1 x 10-3	97.93% (92.86%, 98.74%)	0.00% (0.00%, < 0.01%)
3.16 x 10-3	97.94% (92.87%, 98.75%)	0.00% (0.00%, < 0.01%)
1 x 10-2	97.95% (92.88%, 98.76%)	0.00% (0.00%, < 0.01%)
3.16 x 10-2	97.96% (92.90%, 98.77%)	0.00% (0.00%, < 0.01%)
0.1	97.99% (92.93%, 98.80%)	0.00% (0.00%, < 0.01%)
0.32	98.04% (92.99%, 98.85%)	0.00% (0.00%, < 0.01%)
1	98.30% (93.27%, 99.03%)	0.00% (0.00%, < 0.01%)
3.16	98.70% (93.99%, 99.29%)	0.00% (0.00%, < 0.01%)
10	99.04% (95.02%, 99.51%)	0.00% (0.00%, < 0.01%)
31.6	99.30% (95.96%, 99.67%)	0.00% (0.00%, < 0.01%)
100	99.48% (96.74%, 99.784)	0.00% (0.00%, < 0.01%)
316	99.61% (97.40%, 99.86%)	< 0.01% (0.00%, < 0.01%)
1000	99.71% (97.95%, 99.90%)	< 0.01% (0.00%, 0.010%)
3162	99.79% (98.40%, 99.93%)	< 0.01% (0.00%, 0.01%)
10000	99.84% (98.78%, 99.95%)	< 0.01% (0.00%, 0.02%)
3.16 x 104	99.88% (99.09%, 99.97%)	< 0.01% (0.00%, 0.04%)
1 x 105	99.90% (99.33%, 99.98%)	< 0.01% (0.00%, 0.08%)
3.16 x 105	99.92% (99.51%, 99.98%)	0.01% (0.00%, 0.15%)
1 x 106	99.94% (99.63%, 99.99%)	0.02% (0.00%, 0.30%)
3.16 x 106	99.95% (99.74%, 99.99%)	0.05% (0.00%, 0.65%)
1 x 107	99.96% (99.83%, 99.99%)	0.12% (0.00%, 1.60%)
3.16 x 107	99.97% (99.91%, 99.99%)	0.25% (0.00%, 3.00%)
1 x 108	99.97% (99.94%, > 99.99%)	0.56% (0.00%, 4.57%)
3.16 x 108	99.98% (99.96%, > 99.99%)	1.41% (0.00%, 7.96%)
1 x 109	99.98% (99.97%, > 99.99%)	2.85% (0.05%, 13.60%)
3.16 x 109	99.99% (99.98%, > 99.99%)	10.27% (0.62%, 45.11%)
1 x 1010	100% (99.99%, 100%)	45.74% (8.83%, 86.80%)
3.16 x 1010	100% (> 99.99%, 100%)	85.28% (46.57%, 96.54%)
1 x 1011	100% (> 99.99%, 100%)	97.23% (79.31%, 100%)
3.16 x 1011	100% (100%, 100%)	100% (94.58%, 100%)
1 x 1012	100% (100%, 100%)	100% (100%, 100%)
a Reported as the median (50th percentile), with the 5th and 95th percentiles in parentheses.
b Reported as the median (50th percentile), with the 5th and 95th percentiles in parentheses.

Table 2.—Output from the Model in the FDA/FSIS LmRA Intermediate-Aged Population

Dose (cfu/serving)	Estimated Servings (Cumulative Percentage)a	Estimated Illnesses (Cumulative Percentage)b
0	97.83% (94.30%, 98.70%)	0.00% (0.00%, < 0.01%)
1 x 10-4	97.84% (94.31%, 98.71%)	0.00% (0.00%, < 0.01%)
3.16 x 10-4	97.85% (94.33%, 98.73%)	0.00% (0.00%, < 0.01%)
1 x 10-3	97.87% (94.35%, 98.74%)	0.00% (0.00%, < 0.01%)
3.16 x 10-3	97.89% (94.37%, 98.76%)	0.00% (0.00%, < 0.01%)
1 x 10-2	97.91% (94.39%, 98.78%)	0.00% (0.00%, < 0.01%)
3.16 x 10-2	97.93% (94.40%, 98.79%)	0.00% (0.00%, < 0.01%)
0.1	97.96% (94.43%, 98.81%)	0.00% (0.00%, < 0.01%)
0.32	98.01% (94.47%, 98.86%)	0.00% (0.00%, < 0.01%)
1	98.27% (94.72%, 99.04%)	0.00% (0.00%, < 0.01%)
3.16	98.64% (95.35%, 99.30%)	0.00% (0.00%, < 0.01%)
10	98.97% (96.15%, 99.51%)	0.00% (0.00%, < 0.01%)
31.6	99.22% (96.86%, 99.67%)	0.00% (0.00%, < 0.01%)
100	99.41% (97.51%, 99.77%)	0.00% (0.00%, < 0.01%)
316	99.55% (98.02%, 99.84%)	< 0.01% (0.00%, 0.01%)
1000	99.66% (98.45%, 99.89%)	< 0.01% (0.00%, 0.01%)
3162	99.74% (98.79%, 99.92%)	< 0.01% (0.00%, 0.01%)
10000	99.80% (99.07%, 99.94%)	< 0.01% (0.00%, 0.02%)
3.16 x 104	99.84% (99.29%, 99.96%)	< 0.01% (0.00%, 0.03%)
1 x 105	99.87% (99.46%, 99.97%)	< 0.01% (0.00%, 0.05%)
3.16 x 105	99.90% (99.60%, 99.98%)	0.01% (0.00%, 0.10%)
1 x 106	99.92% (99.70%, 99.98%)	0.02% (0.00%, 0.19%)
3.16 x 106	99.93% (99.78%, 99.99%)	0.04% (0.00%, 0.41%)
1 x 107	99.95% (99.86%, 99.99%)	0.09% (0.00%, 0.97%)
3.16 x 107	99.95% (99.90%, 99.99%)	0.20% (0.00%, 1.81%)
1 x 108	99.96% (99.93%, 100%)	0.45% (0.00%, 2.94%)
3.16 x 108	99.97% (99.95%, 100%)	1.19% (0.00%, 5.24%)
1 x 109	99.98% (99.96%, 100%)	2.29% (0.00%, 10.06%)
3.16 x 109	99.99% (99.97%, 100%)	8.59% (0.10%, 42.98%)
1 x 1010	100% (99.98%, 100%)	43.15% (5.55%, 86.92%)
3.16 x 1010	100% (> 99.99%, 100%)	85.13% (36.41%, 96.46%)
1 x 1011	100% (> 99.99%, 100%)	97.23% (72.09%, 100%)
3.16 x 1011	100% (100%, 100%)	100% (94.14%, 100%)
1 x 1012	100% (100%, 100%)	100% (100%, 100%)
a Reported as the median (50th percentile), with the 5th and 95th percentiles in parentheses.
b Reported as the median (50th percentile), with the 5th and 95th percentiles in parentheses.

Table 3.—Output from the Model in the FDA/FSIS LmRA Neonatal Population

Dose (cfu/serving)	Estimated Servings (Cumulative Percentage)a	Estimated Illnesses (Cumulative Percentage)b
0	97.90% (94.56%, 98.74%)	0.00% (0.00%, < 0.01%)
1 x 10-4	97.91% (94.57%, 98.75%)	0.00% (0.00%, < 0.01%)
3.16 x 10-4	97.92% (94.58%, 98.77%)	0.00% (0.00%, < 0.01%)
1 x 10-3	97.94% (94.59%, 98.79%)	0.00% (0.00%, < 0.01%)
3.16 x 10-3	97.96% (94.61%, 98.80%)	0.00% (0.00%, < 0.01%)
1 x 10-2	97.98% (94.62%, 98.81%)	0.00% (0.00%, < 0.01%)
3.16 x 10-2	98.00% (94.64%, 98.83%)	0.00% (0.00%, < 0.01%)
0.1	98.03% (94.66%, 98.85%)	0.00% (0.00%, < 0.01%)
0.32	98.08% (94.72%, 98.90%)	0.00% (0.00%, < 0.01%)
1	98.33% (94.97%, 99.07%)	0.00% (0.00%, < 0.01%)
3.16	98.68% (95.57%, 99.33%)	0.00% (0.00%, < 0.01%)
10	99.01% (96.31%, 99.52%)	0.00% (0.00%, < 0.01%)
31.6	99.24% (97.01%, 99.67%)	0.00% (0.00%, < 0.01%)
100	99.43% (97.63%, 99.78%)	0.00% (0.00%, < 0.01%)
316	99.57% (98.11%, 99.84%)	< 0.01% (0.00%, < 0.01%)
1000	99.67% (98.52%, 99.89%)	< 0.01% (0.00%, < 0.01%)
3162	99.75% (98.85%, 99.92%)	< 0.01% (0.00%, 0.01%)
10000	99.81% (99.11%, 99.95%)	< 0.01% (0.00%, 0.03%)
3.16 x 104	99.85% (99.32%, 99.96%)	< 0.01% (0.00%, 0.06%)
1 x 105	99.88% (99.48%, 99.97%)	< 0.01% (0.00%, 0.15%)
3.16 x 105	99.90% (99.62%, 99.98%)	0.01% (0.00%, 0.35%)
1 x 106	99.92% (99.71%, 99.98%)	0.02% (0.00%, 0.71%)
3.16 x 106	99.94% (99.79%, 99.99%)	0.06% (0.00%, 1.53%)
1 x 107	99.95% (99.86%, 99.99%)	0.13% (0.00%, 3.26%)
3.16 x 107	99.96% (99.91%, 99.99%)	0.27% (0.00%, 5.81%)
1 x 108	99.97% (99.94%, 99.99%)	0.61% (< 0.01%, 8.72%)
3.16 x 108	99.97% (99.95%, > 99.99%)	1.49% (0.02%, 13.16%)
1 x 109	99.98% (99.96%, > 99.99%)	2.96% (0.19%, 20.08%)
3.16 x 109	99.99% (99.97%, > 99.99%)	11.09% (0.96%, 51.41%)
1 x 1010	> 99.99% (99.98%, > 99.99%)	52.05% (11.25%, 90.05%)
3.16 x 1010	> 99.99% (> 99.99%, 100%)	89.24% (56.05%, 97.60%)
1 x 1011	100% (> 99.99%, 100%)	98.07% (88.20%, 100%)
3.16 x 1011	100% (100%, 100%)	100% (96.51%, 100%)
1 x 1012	100% (100%, 100%)	100% (100%, 100%)
a Reported as the median (50th percentile), with the 5th and 95th percentiles in parentheses.
b Reported as the median (50th percentile), with the 5th and 95th percentiles in parentheses.

Table 4.—Output from the Model in the FDA/FSIS LmRA Total Population

Dose (cfu/serving)	Estimated Servings (Cumulative Percentage)	Estimated Illnesses (Cumulative Percentage)
0	97.85% (94.02%, 98.69%)	0.00% (0.00%, < 0.01%)
1 x 10-4	97.86% (94.03%, 98.71%)	0.00% (0.00%, < 0.01%)
3.16 x 10-4	97.87% (94.05%, 98.72%)	0.00% (0.00%, < 0.01%)
1 x 10-3	97.89% (94.06%, 98.74%)	0.00% (0.00%, < 0.01%)
3.16 x 10-3	97.91% (94.08%, 98.75%)	0.00% (0.00%, < 0.01%)
1 x 10-2	97.92% (94.09%, 98.77%)	0.00% (0.00%, < 0.01%)
3.16 x 10-2	97.93% (94.11%, 98.78%)	0.00% (0.00%, < 0.01%)
0.1	97.96% (94.14%, 98.80%)	0.00% (0.00%, < 0.01%)
0.32	98.01% (94.20%, 98.85%)	0.00% (0.00%, < 0.01%)
1	98.27% (94.44%, 99.04%)	0.00% (0.00%, < 0.01%)
3.16	98.65% (95.11%, 99.30%)	0.00% (0.00%, < 0.01%)
10	98.98% (95.92%, 99.51%)	0.00% (0.00%, < 0.01%)
31.6	99.23% (96.67%, 99.67%)	0.00% (0.00%, < 0.01%)
100	99.42% (97.36%, 99.77%)	0.00% (0.00%, < 0.01%)
316	99.56% (97.89%, 99.85%)	< 0.01% (0.00%, < 0.01%)
1000	99.67% (98.35%, 99.89%)	< 0.01% (0.00%, 0.01%)
3162	99.75% (98.73%, 99.92%)	< 0.01% (0.00%, 0.01%)
10000	99.80% (99.01%, 99.95%)	< 0.01% (0.00%, 0.02%)
3.16 x 104	99.85% (99.25%, 99.96%)	< 0.01% (0.00%, 0.04%)
1 x 105	99.88% (99.43%, 99.97%)	< 0.01% (0.00%, 0.08%)
3.16 x 105	99.90% (99.58%, 99.98%)	0.01% (0.00%, 0.14%)
1 x 106	99.92% (99.69%, 99.98%)	0.02% (0.00%, 0.29%)
3.16 x 106	99.94% (99.77%, 99.99%)	0.05% (0.00%, 0.66%)
1 x 107	99.95% (99.85%, 99.99%)	0.12% (0.00%, 1.64%)
3.16 x 107	99.96% (99.91%, 99.99%)	0.25% (0.00%, 2.75%)
1 x 108	99.97% (99.93%, 99.99%)	0.55% (< 0.01%, 4.20%)
3.16 x 108	99.97% (99.95%, > 99.99%)	1.39% (< 0.01%, 7.33%)
1 x 109	99.98% (99.96%, > 99.99%)	2.73% (0.05%, 12.32%)
3.16 x 109	99.99% (99.97%, > 99.99%)	9.94% (0.58%, 44.23%)
1 x 1010	> 99.99% (99.98%, > 99.99%)	45.52% (8.21%, 86.55%)
3.16 x 1010	> 99.99% (> 99.99%, 100%)	85.45% (44.90%, 96.46%)
1 x 1011	100% (> 99.99%, 100%)	97.18% (77.62%, 100%)
3.16 x 1011	100% (100%, 100%)	100% (94.01%, 100%)
1 x 1012	100% (100%, 100%)	100% (100%, 100.)
a Reported as the median (50th percentile), with the 5th and 95th percentiles in parentheses.
b Reported as the median (50th percentile), with the 5th and 95th percentiles in parentheses.

Table 5.—Annual Incidence of Listeriosis in the National Population Estimated Using the Model in the FDA/FSIS LmRA (50th Percentile)

Dose (cfu/serving)	Corresponding Level (cfu/g) Assuming a 100 g serving	Estimated Number of Cases of Listeriosis Per Year (50th Percentile)
		Elderly	Intermediate-Age	Neonatal	Total Population
0	0	0	0	0	0
1	0.01	0.0	0.0	0.0	0.0
10	0.1	0.0	0.0	0.0	0.0
100	1	0.0	0.0	0.0	0.0
316	3.16	0.0	0.0	0.0	0.0
1,000	10	0.0	0.0	0.0	0.0
3,160	31.6	0.0	0.0	0.0	0.0
10,000	100	0.0	0.0	0.0	0.0
31,600	316	0.0	0.0	0.0	0.0
100,000	1,000	0.0	0.0	0.0	0.1
316,000	3,160	0.1	0.0	0.0	0.1
1,000,000	104	0.1	0.1	0.0	0.3
3,160,000	31,600	0.4	0.2	0.1	0.6
107	105	0.8	0.4	0.2	1.4
3.16 x 107	316,000	1.5	0.7	0.3	2.6
108	106	3.6	1.8	0.7	6.3
3.16 x 108	3.16 x 106	9.9	5.2	1.9	17.5
109	107	16.7	7.7	3.2	27.8
3.16 x 109	3.16 x 107	86.0	44.2	17.6	149.8
1010	108	411.1	242.6	88.5	739.4
3.16 x 1010	3.16 x 108	458.3	294.7	80.3	829.7
1011	109	138.5	84.9	19.1	243.8
3.16 x 1011	3.16 109	32.1	19.5	4.2	58.5
1012	1010	0.0	0.0	0.0	0.0
Total		1159	702	216	2078

Appendix 2.—Modeled Percentage Distribution of Food Servings Contaminated with L. monocytogenes at Time of Consumption for Foods That Do Not Support Growth

Table III-16 in the FDA/FSIS LmRA (see Section III, p. 73) reports the modeled distribution of L. monocytogenes at time of consumption in “dose bins” that combine the distribution of L. monocytogenes for several doses. For example, in Table III-16 the column labeled 1-1,000 cfu/serving includes the combined modeled distributions for doses of 1, 3, 10, 32, 100, 316, and 1,000 cfu/serving. To provide additional information about the distribution at time of consumption of L. monocytogenes in servings of foods that generally do not support its growth, in Table 6 we break the modeled distributions from Table III-16 into more discrete dose bins within the range of 1 cfu/serving to 1,000,000 cfu/serving. In addition, in Table 6 we include a contamination level, in cfu/g, that would be associated with each given dose if there was a uniform serving size of 100 g.

Table 6.—Modeled Percentage Distribution of Food Servings Contaminated with L. monocytogenes at Time of Consumption for Foods That Do Not Support Growth

Food Category	Median Percentage of Food Servings Contaminated with L. monocytogenes at:
	1 cfu/serving (0.01 cfu/ga)	> 1 - 10 cfu/servingb (> 0.01-0.1 cfu/g)	> 10 - 100 cfu/servingc (> 0.1 - 1 cfu/g)	100 to 103 cfu/servingd (> 1 - 10 cfu/g)	> 103 - 104 cfu/servinge (> 10 - 100 cfu/g)	> 104 - 105 cfu/servingf (> 100 - 1,000 cfu/g)	> 105 - 106 cfu/servingg (> 103 - 104 cfu/g)
Seafood
Preserved Fish	0.9 (<0.1, 3.1)h	2.1 (0.1, 8.0)	1.2 (<0.1, 5.8)	0.6 (<0.1, 4.0)	0.2 (<0.1, 2.3)	0.1 (<0.1, 1.2)	0.1 (<0.1, <0.7)
Dairy
Hard Cheese	<0.1 (<0.1, .5)	<0.1 (<0.1, 0.6)	<0.1 (<0.1, 0.4)	<0.1 (<0.1, 0.2)	<0.1 (<0.1, 0.1)	<0.1 (<0.1, <0.1)	<0.1 (<0.1, <0.1)
Processed Cheese	0.2 (<0.1, 0.6)	0.3 (<0.1, 0.9)	0.1 (<0.1, 0.4)	0.1 (<0.1, 0.2)	<0.1 (<0.1, 0.1)	<0.1 (<0.1, 0.1)	<0.1 (<0.1, <0.1)
Ice Cream/Frozen Dairy	0.1 (<0.1, 0.2)	0.2 (0.1, 0.3)	0.1 (<0.1, 0.1)	<0.1 (<0.1, <0.1)	<0.1 (<0.1, <0.1)	<0.1 (<0.1, <0.1)	<0.1 (<0.1, <0.1)
Cultured Milk Products	0.1 (<0.1, 1.1)	0.2 (<0.1, 1.5)	0.1 (<0.1, 0.8)	<0.1 (<0.1, 0.4)	<0.1 (<0.1, 0.2)	<0.1 (<0.1, 0.1)	<0.1 (<0.1, <0.1)
Deli-type salads	1.9 (0.7, 3.7)	3.0 (0.9, 5.2)	1.1 (0.3, 1.9)	0.3 (0.1, 0.7)	0.1 (<0.1, 0.2)	<0.1 (<0.1, 0.1)	<0.1 (<0.1, <0.1)
a Assumes a uniform serving size of 100 g.
b Includes combined estimates for doses of 3.16 and 10 cfu.
c Includes combined estimates for doses of 31.6 and 100 cfu.
d Includes combined estimates for doses of 316 and 1,000 cfu.
e Includes combined estimates for doses of 3160 and 10,000 cfu.
f Includes combined estimates for doses of 31,600 and 100,000 cfu.
g Includes combined estimates for doses of 316,000 and 1,000,000 cfu.
h Numbers in parentheses denote the 5th and 95th percentile uncertainty levels, respectively.

Dated: January 23, 2008.

Margaret O'K. Glavin,

Associate Commissioner for Regulatory Affairs.

Footnotes

1.  See also, e.g., Young v. Community Nutrition Institute, 476 U.S. 974, 982-83 (1986) (citing to United States of America v. Lexington Mill & Elevator Co. as “discussing proper interpretation of the language that became § 342(a)”).

2.  Some of the food categories discussed in this document (e.g., frankfurters) are under the jurisdiction of the Food Safety and Inspection Service (FSIS) of the U.S. Department of Agriculture rather than FDA.

3.  Because normal pasteurization will effectively eliminate L. monocytogenes, it is generally assumed that contamination of products such as pasteurized fluid milk is the result of post-pasteurization contamination (see Section V of Ref. 1, p. 170).

4.  Intrinsic factors include chemical and physical factors that are normally within the structure of the food, e.g., pH and water activity. Extrinsic factors are those that refer to the environment surrounding the food, e.g., storage temperature. Processing factors are those that are deliberately applied to food to achieve improved preservation, such as the addition of acid to lower pH (Ref. 11).

5.  Whether a particular antimicrobial substance is effective in preventing the growth of L. monocytogenes in a given food generally depends on a series of factors. Naturally occurring or added antimicrobial substances can have an interactive or synergistic effect with other parameters of the formulation, such as pH, water activity, the presence of other preservatives, and processing temperature. A concept known as the “hurdle concept” states that several inhibitory factors (hurdles), while individually unable to inhibit microorganisms, will, nevertheless, be effective in combination (Refs. 10 and 15). For reasons such as these, whether the addition of a particular antimicrobial substance to a particular food is effective in preventing the growth of L. monocytogenes is a case-by-case determination, based on available data and information. However, a listeristatic control measure is generally considered to be effective if growth studies show less than one log increase in the number of L. monocytogenes during replicate trials with the food of interest. For an example of how such studies are conducted, see Reference 16.

6.  The examples in this document of foods that generally fall within a given category do not include meat and poultry products because such products are under the jurisdiction of FSIS. Unless otherwise specified, the reference supporting the characterization of the food as to whether it supports the growth of L. monocytogenes is Appendix 8 in Reference 1.

7.  We also have worked with firms who voluntarily decide to recall one or more food products—e.g., when L. monocytogenes is detected by regulatory authorities in the States. However, CPG Sec. 527.300 does not address product recalls.

8.  Under guidelines established by Health Canada for the microbiological safety of food (Ref. 26), a Health 1 concern is one in which action is taken to ensure that the product is no longer sold and the population does not consume what they have at home. A Health 2 concern is one in which action is taken to limit further distribution of the product.

9.  A more virulent strain would have the potential to cause listeriosis with fewer cells than a less virulent strain.

10.  The data in the FDA/FSIS LmRA are reported in terms of cfu/serving. However, it would not be practical from an operational perspective to consider an enforcement policy concerning L. monocytogenes in food in terms of cfu/serving, because each food category has a different serving size. Instead, for purposes of an enforcement policy, we would consider L. monocytogenes in terms of cfu/g of food based on a uniform serving size. For operational purposes, we selected a uniform serving size of 100 g because 100 g approximates the median serving size for several of the food categories that are consumed in relatively large amounts (see Table III-3 in Section III, p. 35 of the FDA/FSIS LmRA). This is a relatively conservative estimate of serving size and increases the relative conservativeness of the enforcement policy.

11.  FAO/WHO includes the elderly, infants, pregnant women and immunocompromised patients in the susceptible population (see Part 1, p. 5 of the FAO/WHO LmRA).

12.  The FDA/FSIS LmRA estimates that Deli-type Salads (a category of food defined in the risk assessment) present a moderate risk of listeriosis. However, the data and analysis presented in the FDA/FSIS LmRA do not distinguish between those Deli-type Salads that support the growth of L. monocytogenes and those that do not support the growth of L. monocytogenes. Regardless of this limitation, the FDA/FSIS LmRA estimates that Deli-type Salads are associated with less than one case of listeriosis per billion servings and less than one case of listeriosis per year (see Figure V-6 in Section V, p. 133 of the FDA/FSIS LmRA). In addition, as shown in Table III-16 of the FDA/FSIS LmRA (see Section III, p. 73) and Appendix 2 of this document, it would be rare to find L. monocytogenes in Deli-type Salads at greater than 100 cfu/g.

13.  The FAO/WHO LmRA estimates that individuals with serious medical conditions (i.e,, transplant and dialysis patients and individuals with certain cancers or AIDS), the perinatal population, and the elderly have higher relative susceptibility than the general population. See the discussion and tables in Part 5, pp. 140-142 of the FAO/WHO LmRA. Appendix 9 of the FDA/FSIS LmRA notes that the population estimated to have the greatest sensitivity (i.e., hospitalized transplant patients) may have experienced listeriosis at levels as low as 5 to 60 cfu/g. However, these patients have a temporary status in that the degree to which individual patients are immunocompromised decreases as time passes relative to the clinical procedure that they undergo. While in this temporary status, they are under active medical care and their diets are carefully controlled—e.g., they are unlikely to be consuming Preserved Fish. In addition, it would be rare to find L. monocytogenes at greater than 10 cfu/g in dairy products that do not support the growth of L. monocytogenes (see Table III-16 of the FDA/FSIS LmRA in Section III, p. 73 and Appendix 2 of this document).

14.  E.g., the draft CPG advises FDA staff to use ISO 11290-2:1998(E) “Microbiology of food and animal feeding stuffs—Horizontal method for the detection and enumeration of Listeria monocytogenes—Part 2: Enumeration method” as the method for enumerating L. monocytogenes. ISO methods are available from the International Organization for Standardization at http://www.iso.org/​iso/​en/​ISOOnline.frontpage.