Draft Compliance Policy Guide Sec. 555.320 Listeria monocytogenes, 7298-7310 [08-549]
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Federal Register / Vol. 73, No. 26 / Thursday, February 7, 2008 / Notices
food as well as surfaces that do not
contact food), very few would have a
program in place as thorough as the one
described in the draft guidance.
Therefore, FDA estimates that 4,270
establishments may choose to adopt the
recommendations to develop a written
environmental monitoring program,
keep environmental testing results, and
record finished product testing results.
Developing a written environmental
monitoring program would be a onetime cost and we assume that it would
take approximately 8 hours. This results
in a first year burden of about 34,160
hours (4,270 plants x 8 hours). For
critical food-contact surfaces, the draft
guidance recommends that tests be
conducted on a weekly basis. We
assume that it would take up to half an
hour to produce a record of the results
of the test, depending on the number of
sites tested and subject to variability
between firms, resulting in an annual
burden of about 111,020 hours ((4,270
plants) x (52 records per year) x (0.5
hours)). For critical non-food-contact
surfaces, the draft guidance
recommends that tests be conducted
every 2 weeks. As with testing for foodcontact surfaces, we assume that the
records would take up to half an hour
to produce, resulting in an annual
burden of about 55,510 hours ((4,270
plants) x (26 records per year) x (0.5
hours)). The draft guidance recommends
‘‘periodic’’ testing of finished product,
such as weekly, monthly, or quarterly.
For purposes of this analysis, FDA
assumes most firms would conduct
monthly testing of finished product. As
with testing of critical surfaces, we
assume the records would take
approximately one half hour to produce,
for an annual burden of about 25,620
hours ((4,270 plants) x (12 records per
year) x (0.5 hours)).
In the draft guidance, FDA is
recommending that firms that detect
Listeria species on critical surfaces or in
the finished product take corrective
action and keep a record of what was
done. The time to record the corrective
actions would vary, but on average FDA
estimates the record would require one
half hour to produce. FDA cannot
accurately predict how often firms
would detect Listeria species in the
environment. For the purposes of this
analysis, and assuming that firms follow
the rest of the guidance, FDA
conservatively assumes that firms
would detect Listeria species on foodcontact surfaces about 20 percent of the
time that tests are run, producing a total
of 10 new records per establishment
annually. Because non-food-contact
surfaces cover inherently more space
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than food-contact surfaces and may be
cleaned less stringently, FDA estimates
that firms would detect Listeria species
twice as often per test as they do when
running tests on food-contact surfaces.
Because these tests are run only half as
often as food-contact surface tests (every
2 weeks rather than every week), this
record would also be produced an
average of 10 times annually per
establishment. We assume that Listeria
species would not often be detected in
the final product, based on the
projections of the ‘‘Quantitative
Assessment of Relative Risk to Public
Health From Foodborne Listeria
monocytogenes Among Selected
Categories of Ready-to-Eat Foods,’’ (the
Risk Assessment), written jointly by
USDA and FDA. The Risk Assessment
projected that 2 percent of RF-RTE food
is contaminated with L. monocytogenes.
FDA uses this number to estimate that
records for corrective action due to
finished product testing would produce,
on average, 0.2 new records per
establishment annually. The total
annual burden produced by corrective
action records would be about 43,127
hours ([(4,270 plants) x (10 records per
year for corrective actions taken after
food-contact surface positive) x (0.5
hours per record)] + [(4,270 plants) x (10
records per year) x (0.5 hours per record
for corrective actions taken after nonfood-contact surface positive )] + ((4,270
plants) x (0.2 records per year for
corrective actions after finished product
positive) x (0.5 hours per record)]).
If a firm does not use one of the
methods described in FDA’s BAM or by
ISO, FDA is recommending that the firm
have a written record of its method to
enumerate or detect L. monocytogenes.
FDA assumes most firms would use one
of the methods described in the BAM or
by ISO. Therefore, there would be no
new collection of information.
FDA estimates that record
maintenance would require roughly 1
hour per week for each firm, for a total
of about 222,040 annual hours ((4,270
plants) x (52 weeks maintenance) x (1
hour per week)).
FDA estimates that each of the 4,270
establishments expected to keep new
records would purchase a storage unit
for the records. A standard file cabinet
large enough for such records as
described in the guidance costs about
$150. Therefore, there would be total
first year capital costs of about $640,500
(4,270 plants x $150).
III. Comments
Interested persons may submit to the
Division of Dockets Management (see
ADDRESSES) written or electronic
comments regarding the draft guidance
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and the collection of information
provisions. Submit a single copy of
electronic comments or two paper
copies of any mailed comments, except
that individuals may submit one paper
copy. Comments are to be identified
with the docket number found in
brackets in the heading of this
document. The draft guidance and
received comments may be seen in the
Division of Dockets Management
between 9 a.m. and 4 p.m., Monday
through Friday.
Please note that on January 15, 2008,
the FDA Web site transitioned to the
Federal Dockets Management System
(FDMS). FDMS is a Government-wide,
electronic docket management system.
Electronic submissions will be accepted
by FDA through the FDMS only.
IV. Electronic Access
Persons with access to the Internet
may obtain the draft guidance from the
Center for Food Safety and Applied
Nutrition home page at https://
www.cfsan.fda.gov/guidance.html.
Dated: January 16, 2008.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 08–548 Filed 2–6–08; 8:45 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2008–D–0058]
Draft Compliance Policy Guide Sec.
555.320 Listeria monocytogenes; Notice
of Public Meeting
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
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Federal Register / Vol. 73, No. 26 / Thursday, February 7, 2008 / Notices
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.
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 https://
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: 202–479–6801, e-mail:
isabelle_howes@grad.usda.gov.
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:
Juanita.Yates@fda.hhs.gov.
ADDRESSES:
SUPPLEMENTARY INFORMATION:
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 https://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
https://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.
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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).
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
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7299
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 outbreakassociated 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
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)’’).
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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
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).
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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:
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.
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• 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
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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).
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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
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.
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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.
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.
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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
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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 doseresponse 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 107.5 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
9 A more virulent strain would have the potential
to cause listeriosis with fewer cells than a less
virulent strain.
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(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., 1010.5 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 104.5 cfu/serving
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).
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(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 105.5 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 106.5 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
101.5 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
102.5 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
103.5 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
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.
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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
monocytogenes and those that do not support the
growth of L. monocytogenes. Regardless of this
limitation, the FDA/FSIS LmRA estimates that Delitype 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
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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.
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 https://www.iso.org/iso/en/
ISOOnline.frontpage.
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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 https://
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
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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 https://
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 https://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.
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Beckman, Custom Cuts Co., March 5, 1999.
Available at https://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
https://www.cfsan.fda.gov/~ebam/bam10.html. Accessed and printed on April 10,
2007.
25. Health Canada, ‘‘Policy on Ready-to-Eat
Foods Contaminated with Listeria
monocytogenes,’’ 2004. Available at https://
www.hc-sc.gc.ca/fn-an/alt_formats/hpfbdgpsa/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 https://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 https://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
https://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 https://www.who.int/
foodsafety/publications/micro/mra_listeria/
en/. 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
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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 retabulated 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.
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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
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
jlentini on PROD1PC65 with NOTICES
0
100% (100%, 100%)
100% (94.58%, 100%)
1 x 1012
100% (100%, 100%)
100% (100%, 100%)
a Reported
b Reported
VerDate Aug<31>2005
as the median (50th percentile), with the 5th and 95th percentiles in parentheses.
as the median (50th percentile), with the 5th and 95th percentiles in parentheses.
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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
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
jlentini on PROD1PC65 with NOTICES
0
100% (100%, 100%)
100% (94.14%, 100%)
1 x 1012
100% (100%, 100%)
100% (100%, 100%)
a Reported
b Reported
VerDate Aug<31>2005
as the median (50th percentile), with the 5th and 95th percentiles in parentheses.
as the median (50th percentile), with the 5th and 95th percentiles in parentheses.
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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
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
jlentini on PROD1PC65 with NOTICES
0
100% (100%, 100%)
100% (96.51%, 100%)
1 x 1012
100% (100%, 100%)
100% (100%, 100%)
a Reported
b Reported
VerDate Aug<31>2005
as the median (50th percentile), with the 5th and 95th percentiles in parentheses.
as the median (50th percentile), with the 5th and 95th percentiles in parentheses.
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TABLE 4.—OUTPUT FROM THE MODEL IN THE FDA/FSIS LMRA TOTAL POPULATION
Dose (cfu/serving)
Estimated Servings (Cumulative Percentage)
Estimated Illnesses (Cumulative Percentage)
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
jlentini on PROD1PC65 with NOTICES
0
100% (100%, 100%)
100% (94.01%, 100%)
1 x 1012
100% (100%, 100%)
100% (100%, 100.)
a Reported
b Reported
VerDate Aug<31>2005
as the median (50th percentile), with the 5th and 95th percentiles in parentheses.
as the median (50th percentile), with the 5th and 95th percentiles in parentheses.
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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
0
Elderly
0
1
Estimated Number of Cases of Listeriosis Per Year (50th Percentile)
Intermediate-Age
Neonatal
Total Population
0
0
0
0
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
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
1159
702
216
2078
3.16 x
107
Total
Appendix 2.—Modeled Percentage
Distribution of Food Servings
Contaminated with L. monocytogenes at
Time of Consumption for Foods That
Do Not Support Growth
jlentini on PROD1PC65 with NOTICES
Table III–16 in the FDA/FSIS LmRA
(see Section III, p. 73) reports the
modeled distribution of L.
monocytogenes at time of consumption
VerDate Aug<31>2005
17:02 Feb 06, 2008
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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
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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.
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TABLE 6.—MODELED PERCENTAGE DISTRIBUTION OF FOOD SERVINGS CONTAMINATED WITH L. monocytogenes AT TIME
OF CONSUMPTION FOR FOODS THAT DO NOT SUPPORT GROWTH
Median Percentage of Food Servings Contaminated with L. monocytogenes at:
> 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)
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)
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)
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)
Food Category
1 cfu/serving
(0.01 cfu/ga)
Seafood
Preserved Fish
Dairy
Deli-type salads
a Assumes
a uniform serving size of 100 g.
combined estimates for doses of 3.16 and 10 cfu.
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.
b Includes
c Includes
Dated: January 23, 2008.
Margaret O’K. Glavin,
Associate Commissioner for Regulatory
Affairs.
[FR Doc. 08–549 Filed 2–6–08; 8:45 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
Radiological Devices Panel of the
Medical Devices Advisory Committee;
Notice of Meeting
AGENCY:
Food and Drug Administration,
HHS.
jlentini on PROD1PC65 with NOTICES
ACTION:
Notice.
This notice announces a forthcoming
meeting of a public advisory committee
of the Food and Drug Administration
(FDA). At least one portion of the
meeting will be closed to the public.
Name of Committee: Radiological
Devices Panel of the Medical Devices
Advisory Committee.
General Function of the Committee:
To provide advice and
recommendations to the agency on
FDA’s regulatory issues.
VerDate Aug<31>2005
17:02 Feb 06, 2008
Jkt 214001
Date and Time: The meeting will be
held on March 4, 2008, from 8 a.m. to
5:30 p.m., and March 5, 2008, from 8
a.m. to 5 p.m.
Location: Hilton Washington DC
North/Gaithersburg, Salons A, B, and C,
620 Perry Pkwy., Gaithersburg, MD.
Contact Person: Nancy Wersto, Center
for Devices and Radiological Health
(HFZ–470), Food and Drug
Administration, 9200 Corporate Blvd.,
Rockville, MD 20850, 240–276–3666, or
FDA Advisory Committee Information
Line, 1–800–741–8138 (301–443–0572
in the Washington, DC area), code
3014512526. Please call the Information
Line for up-to-date information on this
meeting. A notice in the Federal
Register about last minute modifications
that impact a previously announced
advisory committee meeting cannot
always be published quickly enough to
provide timely notice. Therefore, you
should always check the agency’s Web
site and call the appropriate advisory
committee hot line/phone line to learn
about possible modifications before
coming to the meeting.
Agenda: On March 4 and 5, 2008, the
committee intends to discuss and make
recommendations about computer aided
detection and diagnosis (CAD) devices
PO 00000
Frm 00068
Fmt 4703
Sfmt 4703
for radiological images, e.g.,
mammograms, chest x-rays, and
computed tomography (CT) images of
the lungs or colon. There will be a
general discussion focusing on the
general methodologies for CAD,
including how CAD devices are used in
clinical decision-making, how the
devices are tested, and the information
needed to properly assess their safety
and effectiveness. The general
discussion will be followed by specific
discussions related to mammography
CAD devices, colon CAD devices, and
lung CAD devices. These discussions
will include how the different types of
CAD devices are used and the literature
published regarding these devices, with
focus on testing issues related to the
different devices.
FDA intends to make background
material available to the public no later
than 2 business days before the meeting.
If FDA is unable to post the background
material on its Web site prior to the
meeting, the background material will
be made publicly available at the
location of the advisory committee
meeting, and the background material
will be posted on FDA’s Web site after
the meeting. Background material is
available at https://www.fda.gov/ohrms/
E:\FR\FM\07FEN1.SGM
07FEN1
]]>Agencies
[Federal Register Volume 73, Number 26 (Thursday, February 7, 2008)]
[Notices]
[Pages 7298-7310]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 08-549]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2008-D-0058]
Draft Compliance Policy Guide Sec. 555.320 Listeria
monocytogenes; Notice of Public Meeting
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
[[Page 7299]]
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 https://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: 202-479-6801,
e-mail: isabelle_howes@grad.usda.gov.
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: Juanita.Yates@fda.hhs.gov.
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 https://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 https://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).
---------------------------------------------------------------------------
\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 Sec. 342(a)'').
---------------------------------------------------------------------------
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
[[Page 7300]]
unpasteurized milk, frankfurters,\2\ deli meats, and butter) that are
RTE. (Ref. 1).
---------------------------------------------------------------------------
\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.
---------------------------------------------------------------------------
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 milk\3\ (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).
---------------------------------------------------------------------------
\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).
---------------------------------------------------------------------------
Some foods (such as ice cream and pickled fish) are characterized
by intrinsic or extrinsic factors\4\ 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:
---------------------------------------------------------------------------
\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).
---------------------------------------------------------------------------
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\
---------------------------------------------------------------------------
\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.
---------------------------------------------------------------------------
Examples of RTE foods that generally are considered to not support
the growth of L. monocytogenes include:\6\
---------------------------------------------------------------------------
\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.
---------------------------------------------------------------------------
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
[[Page 7301]]
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\
---------------------------------------------------------------------------
\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.
---------------------------------------------------------------------------
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
concern\8\ 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.
---------------------------------------------------------------------------
\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.
---------------------------------------------------------------------------
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
[[Page 7302]]
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 10\10\
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., 10\10\ cfu/serving).
---------------------------------------------------------------------------
\9\ A more virulent strain would have the potential to cause
listeriosis with fewer cells than a less virulent strain.
---------------------------------------------------------------------------
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 10\5\ cfu/serving (corresponding to 10\3\ 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 10\7\ cfu/serving or
less (corresponding to 10\5\ 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 10\8\ cfu/
serving (corresponding to 10\6\ cfu/g for a 100 g serving of food).
Above doses of 10\8\ cfu/serving, the estimated median number of cases
of listeriosis in the total population per year increases
exponentially.
---------------------------------------------------------------------------
\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.
---------------------------------------------------------------------------
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 population\11\ if all servings of RTE foods were at or
below 10\4.5\ cfu/serving (corresponding to 10\3\ 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 10\4\ 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 10\5\ 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 10\2\ cfu/g for a 31.6 g serving of food).
---------------------------------------------------------------------------
\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).
---------------------------------------------------------------------------
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
[[Page 7303]]
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).
---------------------------------------------------------------------------
\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.
---------------------------------------------------------------------------
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\
---------------------------------------------------------------------------
\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 https://
www.iso.org/iso/en/ISOOnline.frontpage.
---------------------------------------------------------------------------
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 https://
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
[[Page 7304]]
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 https://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 https://
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
https://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 https://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 https://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 https://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 https://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 https://
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 https://www.who.int/foodsafety/
publications/micro/mra_listeria/en/. 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.
[[Page 7305]]
Table 1.--Output from the Model in the FDA/FSIS LmRA Elderly Population
----------------------------------------------------------------------------------------------------------------
Estimated Servings (Cumulative Estimated Illnesses (Cumulative
Dose (cfu/serving) Percentage)\a\ 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 10\4\ 99.88% (99.09%, 99.97%) < 0.01% (0.00%, 0.04%)
----------------------------------------------------------------------------------------------------------------
1 x 10\5\ 99.90% (99.33%, 99.98%) < 0.01% (0.00%, 0.08%)
----------------------------------------------------------------------------------------------------------------
3.16 x 10\5\ 99.92% (99.51%, 99.98%) 0.01% (0.00%, 0.15%)
----------------------------------------------------------------------------------------------------------------
1 x 10\6\ 99.94% (99.63%, 99.99%) 0.02% (0.00%, 0.30%)
----------------------------------------------------------------------------------------------------------------
3.16 x 10\6\ 99.95% (99.74%, 99.99%) 0.05% (0.00%, 0.65%)
----------------------------------------------------------------------------------------------------------------
1 x 10\7\ 99.96% (99.83%, 99.99%) 0.12% (0.00%, 1.60%)
----------------------------------------------------------------------------------------------------------------
3.16 x 10\7\ 99.97% (99.91%, 99.99%) 0.25% (0.00%, 3.00%)
----------------------------------------------------------------------------------------------------------------
1 x 10\8\ 99.97% (99.94%, > 99.99%) 0.56% (0.00%, 4.57%)
----------------------------------------------------------------------------------------------------------------
3.16 x 10\8\ 99.98% (99.96%, > 99.99%) 1.41% (0.00%, 7.96%)
----------------------------------------------------------------------------------------------------------------
1 x 10\9\ 99.98% (99.97%, > 99.99%) 2.85% (0.05%, 13.60%)
----------------------------------------------------------------------------------------------------------------
3.16 x 10\9\ 99.99% (99.98%, > 99.99%) 10.27% (0.62%, 45.11%)
----------------------------------------------------------------------------------------------------------------
1 x 10\10\ 100% (99.99%, 100%) 45.74% (8.83%, 86.80%)
----------------------------------------------------------------------------------------------------------------
3.16 x 10\10\ 100% (> 99.99%, 100%) 85.28% (46.57%, 96.54%)
----------------------------------------------------------------------------------------------------------------
1 x 10\11\ 100% (> 99.99%, 100%) 97.23% (79.31%, 100%)
----------------------------------------------------------------------------------------------------------------
3.16 x 10\11\ 100% (100%, 100%) 100% (94.58%, 100%)
----------------------------------------------------------------------------------------------------------------
1 x 10\12\ 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.
[[Page 7306]]
Table 2.--Output from the Model in the FDA/FSIS LmRA Intermediate-Aged Population
----------------------------------------------------------------------------------------------------------------
Estimated Servings (Cumulative Estimated Illnesses (Cumulative
Dose (cfu/serving) Percentage)\a\ 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 10\4\ 99.84% (99.29%, 99.96%) < 0.01% (0.00%, 0.03%)
----------------------------------------------------------------------------------------------------------------
1 x 10\5\ 99.87% (99.46%, 99.97%) < 0.01% (0.00%, 0.05%)
----------------------------------------------------------------------------------------------------------------
3.16 x 10\5\ 99.90% (99.60%, 99.98%) 0.01% (0.00%, 0.10%)
----------------------------------------------------------------------------------------------------------------
1 x 10\6\ 99.92% (99.70%, 99.98%) 0.02% (0.00%, 0.19%)
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