oversight

Food Safety: Preslaughter Interventions Could Reduce E. coli in Cattle

Published by the Government Accountability Office on 2012-03-09.

Below is a raw (and likely hideous) rendition of the original report. (PDF)

             United States Government Accountability Office

GAO          Report to the Secretary of Agriculture




March 2012
             FOOD SAFETY

             Preslaughter
             Interventions Could
             Reduce E. coli in
             Cattle




GAO-12-257
                                               March 2012

                                               FOOD SAFETY
                                               Preslaughter Interventions Could Reduce E. coli in
                                               Cattle
Highlights of GAO-12-257, a report to the
Secretary of Agriculture




Why GAO Did This Study                         What GAO Found
                                               U.S. Department of Agriculture (USDA) and university researchers identified
Since 2006, the U.S. beef industry has         several treatments administered before cattle are slaughtered, or preslaughter
recalled over 23 million pounds of beef        interventions, that could reduce Shiga toxin-producing Escherichia coli (STEC) in
owing to contamination from                    cattle. Such preslaughter interventions include bacteriophages (viruses that infect
pathogenic strains of Shiga toxin-             and kill bacteria), probiotics (live bacteria that can benefit the digestive system),
producing Escherichia coli (STEC)
                                               vaccines (biological preparations that alter the immune system), and sodium
bacteria. These strains do not harm
                                               chlorate (chemical that kills the STEC O157:H7 strain). However, few
cattle but may contaminate meat
during slaughter. If humans eat                manufacturers have submitted applications for preslaughter intervention products
contaminated meat without properly             to target STEC according to officials from USDA and the Food and Drug
cooking it, STEC can cause illnesses,          Administration. One exception is for vaccines to reduce STEC O157:H7.
including bloody diarrhea and                  For preslaughter interventions, USDA exercises responsibilities for licensing and
Hemolytic Uremic Syndrome, which is            regulating STEC vaccines. However, USDA’s approval requirements for these
characterized by kidney failure and can        vaccines are unclear, according to some industry representatives. Specifically,
be fatal. The Departments of Health
                                               USDA’s general guidance does not address some of the unique challenges faced
and Human Services (HHS) and of
                                               by manufacturers of animal health products seeking STEC vaccine approval. For
Agriculture (USDA) play a role in
reducing STEC. USDA stated that
                                               example, the guidance does not explain that, if studies conducted in the
interventions to reduce STEC before            laboratory are insufficient to demonstrate efficacy, the manufacturer would also
slaughter offer a significant opportunity      need to demonstrate that the vaccine is effective in a field setting such as a
to improve food safety.                        feedlot. In contrast, the Canadian Centre for Veterinary Biologics provides more
                                               specific guidance about when it requires the use of laboratory or field studies to
GAO reviewed (1) interventions before          demonstrate efficacy for vaccine license applications. Without guidance that
slaughter that may help reduce STEC            gives manufacturers clear and more specific information they need to submit for
in cattle; (2) USDA’s role in approving        an acceptable application, the approval process for STEC vaccines could face
STEC vaccines; (3) the extent to which
                                               potential delays.
STEC strains have been determined to
be adulterants in beef and the status of       In addition to STEC O157:H7, which it stated in 1994 was an adulterant—a
tests to detect them; and (4) practices,       substance that renders food injurious to human health—in September 2011,
if any, other countries have employed          USDA determined that six other STEC strains were adulterants in raw ground
that could reduce STEC in cattle and           beef and beef trim (meat left after steaks and roasts are cut from beef). USDA
may be relevant to U.S. efforts. GAO           has tests for these six strains and plans to use them in slaughter plants starting
reviewed documents; visited cattle             in June 2012. However, it may be difficult and time-consuming to confirm positive
feedlots and a slaughter plant; and            test results because certain test components are either not commercially
interviewed agency officials,                  available for all strains or do not always provide clear results. USDA is working to
researchers, and industry and
                                               improve the tests and to find a commercial supplier for one key test component.
consumer group representatives with
                                               Also, a few companies voluntarily test for these strains.
expertise in STEC in cattle.
                                               Some foreign governments have practices that could be relevant to U.S. efforts
What GAO Recommends                            to reduce STEC in cattle such as the following:
GAO recommends, among other                         • The European Parliament and the Council of the European Union require
things, that USDA provide more                         certain measures, such as verification of cleanliness by an inspector, to
specific public guidance on the license                ensure that the cattle going to slaughter are clean. In contrast, USDA
approval requirements of STEC                          assesses the health of cattle but does not inspect for cleanliness.
vaccines. USDA neither agreed nor                   • At least 12 European Union member countries collected and reported
disagreed with this recommendation.                    data on STEC in live cattle in 2009. USDA has conducted STEC testing
                                                       in live cattle, but has not tested since 1999.
                                                    • When a person becomes ill from E. coli in Sweden, government officials
View GAO-12-257 or key components.
For more information, contact Lisa Shames at
                                                       try to determine the specific farm that sold the contaminated cattle so
(202) 512-3841 or shamesl@gao.gov.                     that other carcasses from the farm can be tested for STEC. USDA does
                                                       not trace the STEC source back to the farm.
                                                                                        United States Government Accountability Office
Contents


Letter                                                                                       1
               Background                                                                   3
               Several Interventions Could Reduce STEC in Cattle                            8
               USDA Exercises Responsibility for Approving STEC Vaccines, but
                 Its Approval Requirements Are Unclear                                     14
               USDA Determined That Six Additional STEC Strains Were
                 Adulterants and Has Tests to Detect Them                                  16
               Some Countries Have Practices That Could Be Relevant to U.S.
                 Efforts to Reduce STEC in Cattle                                          20
               Conclusions                                                                 22
               Recommendations for Executive Action                                        22
               Agency Comments and Our Evaluation                                          22

Appendix I     Objectives, Scope, and Methodology                                          25



Appendix II    Comments from the U. S. Department of Agriculture                           27



Appendix III   GAO Contact and Staff Acknowledgments                                       29



Tables
               Table 1: Agencies with Responsibilities Related to STEC
                        Contamination in Beef                                               6
               Table 2: Approval Status and Challenges for Preslaughter
                        Interventions                                                      12


Figures
               Figure 1: STEC O157:H7 Bacteria                                              4
               Figure 2: Beef Production Process                                            7
               Figure 3: Preliminary and Isolation and Confirmation Testing
                        Phases for the Six STEC Non-O157 Strains                           19




               Page i                                  GAO-12-257 E. coli Contamination in Beef
Abbreviations

APHIS             Animal and Plant Health Inspection Service
ARS               Agriculture Research Service
CDC               Centers for Disease Control and Prevention
FDA               Food and Drug Administration
FSIS              Food Safety and Inspection Service
HACCP             Hazard Analysis and Critical Control Point
HHS               Department of Health and Human Services
NIFA              National Institute of Food and Agriculture
STEC              Shiga Toxin-Producing Escherichia coli
USDA              U.S. Department of Agriculture




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Page ii                                           GAO-12-257 E. coli Contamination in Beef
United States Government Accountability Office
Washington, DC 20548




                                   March 9, 2012

                                   The Honorable Thomas J. Vilsack
                                   Secretary of Agriculture

                                   Dear Mr. Secretary:

                                   Since 2006, the U.S. beef industry has recalled over 23 million pounds of
                                   beef because of contamination from pathogenic strains of Shiga toxin-
                                   producing Escherichia coli (STEC). These bacterial STEC strains can live
                                   in the intestines or on the hide of cattle without harming them, but they
                                   may contaminate meat during the slaughter process. If humans then
                                   consume the contaminated meat without properly cooking it, STEC
                                   strains can cause illnesses, including bloody diarrhea and Hemolytic
                                   Uremic Syndrome, which is characterized by kidney failure and can be
                                   fatal. The Centers for Disease Control and Prevention (CDC) does not
                                   have estimates specific to beef, but it estimates that STEC contamination
                                   of food consumed domestically causes approximately 176,000 illnesses,
                                   2,400 hospitalizations, and 20 deaths annually. Illnesses caused by
                                   STEC O157:H7, the most common STEC strain in the United States, cost
                                   those infected $489 million annually, in 2010 dollars, according to an
                                   estimate from the U.S. Department of Agriculture (USDA).

                                   In addition to STEC O157:H7, over 150 other STEC strains can cause
                                   illness. In this report, we refer to these strains as STEC non-O157, and
                                   CDC has identified six common groups of such strains that cause
                                   approximately 113,000 illnesses in the United States each year. These
                                   strains are known as O26, O45, O103, O111, O121, and O145.

                                   USDA’s Food Safety and Inspection Service (FSIS) is responsible for
                                   examining and inspecting the carcasses and parts of cattle at slaughter
                                   plants and meat processing plants that will be used for human
                                   consumption. The Federal Meat Inspection Act prohibits the sale of
                                   adulterated meat or meat products—products bearing or containing a
                                   poisonous or deleterious substance that may render them injurious to
                                   human health, among other things—and provides FSIS with the authority
                                   to prescribe rules and regulations concerning the sanitation at slaughter
                                   plants and meat-processing plants. In 1994, FSIS stated that it
                                   considered STEC O157:H7 an adulterant in ground beef, which according
                                   to a USDA report, is the most frequently implicated source of STEC
                                   O157:H7 outbreaks in the United States. FSIS’s inspection authority does
                                   not extend to the feedlot, where most cattle are fed grain for about 140


                                   Page 1                                   GAO-12-257 E. coli Contamination in Beef
days prior to slaughter, but the agency encourages beef producers to use
preslaughter interventions, such as vaccinating the animal against STEC,
to control STEC O157:H7. FSIS has stated that such interventions offer a
significant opportunity to improve food safety because they may reduce
the level of STEC entering the slaughter plant. The beef industry
generally supports researching and developing these interventions and
has funded many intervention activities for possible future use.

In this context, we reviewed USDA’s and others’ efforts to reduce STEC
contamination in beef. Our objectives were to identify (1) preslaughter
interventions—that is, treatments administered before cattle are
slaughtered that can target STEC—that may help reduce STEC in cattle;
(2) USDA’s role in approving STEC vaccines; (3) the extent to which
STEC strains have been determined to be adulterants in beef and the
status of tests to detect them; and (4) practices, if any, other countries
have employed that could reduce STEC in cattle and may be relevant to
U.S. efforts.

For all four objectives, we visited several cattle feedlots and a cattle
slaughter plant in Colorado, which we selected because it is one of the
largest beef producing states, and interviewed USDA officials, beef
industry representatives, and university researchers in Colorado. In
addition, using a nonprobability sample, we conducted a total of 71
interviews with USDA, CDC, and Food and Drug Administration (FDA)
officials; foreign government officials; beef industry representatives;
manufacturers of animal health products; federal and university
researchers; and consumer group representatives with expertise in STEC
in cattle. Because this was a nonprobability sample, the results cannot be
generalized to the entire United States, but can provide examples of
research conducted on preslaughter interventions. To determine the
preslaughter interventions that may help reduce STEC in cattle, we
reviewed USDA and academic studies on preslaughter interventions,
reviewed USDA documents on funding for STEC research, and met with
USDA and university researchers and beef and pharmaceutical industry
representatives. To determine USDA’s role in approving STEC vaccines,
we reviewed USDA guidance and interviewed USDA officials,
manufacturers of animal health products, and university researchers. To
determine the extent to which STEC strains have been determined to be
adulterants in beef and the status of tests to detect them, we reviewed
USDA documents on STEC detection tests and interviewed FDA and
USDA officials, beef industry representatives, and detection test
manufacturers. To determine practices, if any, other countries have
employed that could reduce STEC in cattle and may be relevant to U.S.


Page 2                                   GAO-12-257 E. coli Contamination in Beef
                           efforts, we asked CDC, FDA, and USDA officials; beef industry
                           representatives; university researchers; and consumer group
                           representatives if they were aware of any such practices. We also
                           reviewed international studies, guidance, and requirements for food
                           safety in beef and interviewed international food safety officials. Appendix
                           I contains an expanded explanation of our objectives, scope, and
                           methodology.

                           We conducted this performance audit from January 2011 to March 2012
                           in accordance with generally accepted government auditing standards.
                           Those standards require that we plan and perform the audit to obtain
                           sufficient, appropriate evidence to provide a reasonable basis for our
                           findings and conclusions based on our audit objectives. We believe that
                           the evidence obtained provides a reasonable basis for our findings and
                           conclusions based on our audit objectives.


                           This section discusses STEC and agencies that play a role in reducing
Background                 STEC contamination.


Shiga Toxin-Producing E.   E. coli bacteria live in the intestines of healthy cattle and have a symbiotic
coli                       relationship with the cattle, an association in which the E. coli derives the
                           benefit, and cattle are not harmed. The organism has been found in
                           young beef calves and older cows, as well as in dairy calves and dairy
                           cows. E. coli tends to colonize at the end of a cow’s intestinal system, in
                           an area known as the anorectal junction. A cow with E. coli in its intestinal
                           system typically “sheds” the organism through its feces. As cattle shed
                           E. coli, the bacteria can contaminate the hides and then the meat as the
                           cattle are slaughtered. Several strains of E. coli have evolved to being
                           highly pathogenic and capable of causing death when they infect
                           humans.

                           STEC O157:H7, pictured in figure 1, is the strain of STEC bacteria of
                           primary interest to USDA and researchers. STEC O157:H7 was first
                           recognized as a disease-causing organism in 1982 and became a
                           research priority in 1993, when over 700 people were affected after eating
                           undercooked hamburgers at a fast-food restaurant chain. This outbreak
                           was the largest reported outbreak in North America, and 55 patients,
                           including 4 children who died, developed Hemolytic Uremic Syndrome.
                           Symptoms of STEC O157:H7 can also include severe bloody diarrhea,
                           profuse bleeding, seizures, kidney failure, coma, and death.



                           Page 3                                     GAO-12-257 E. coli Contamination in Beef
Figure 1: STEC O157:H7 Bacteria




In 1994, USDA’s FSIS made public that it considered STEC O157:H7 as
an adulterant in raw ground beef; it established a zero-tolerance policy for
this pathogen in this food product and began a sampling program to test
for the pathogen in federally inspected establishments and retail stores.
FSIS also made public that it would use available enforcement tools, such
as requesting a recall from beef producers if the product had entered
commerce. Any raw ground beef found to contain STEC O157:H7 must
be disposed of or sent for further processing that involves a “lethality
step,” such as cooking the meat before selling it. 1

Under current law, thousands of FSIS regulatory inspectors maintain
continuous inspection at slaughter facilities and examine all slaughtered
meat carcasses. Inspectors also visit other meat-processing facilities at
least once each operating day. In 1996, FSIS established Hazard



1
 According to FSIS, thorough cooking of ground beef to an internal temperature of 160° F
throughout kills STEC O157:H7.




Page 4                                           GAO-12-257 E. coli Contamination in Beef
                            Analysis and Critical Control Point (HACCP) system requirements for all
                            processing plants. The HACCP system requires that plants identify
                            biological, chemical, and physical food safety hazards that are reasonably
                            likely to occur and develop and implement plans to prevent and control
                            those hazards.

                            In addition to STEC O157:H7, CDC has identified six groups of STEC
                            strains—O26, O45, O103, O111, O121, and O145—that are also
                            pathogenic. These STEC non-O157 strains have been found in ground
                            beef and on cattle hides and feces at levels comparable to those for
                            STEC O157:H7, and they have been found to cause the same human
                            illnesses. In 2010, for the first time, the number of laboratory-confirmed
                            STEC infections from strains other than STEC O157:H7 was greater than
                            the number of STEC O157:H7 infections.


Agencies that Play a Role   Two federal departments are primarily responsible for ensuring the safety
in Reducing STEC            of the U.S. food supply, including the prevention of STEC
Contamination               contamination—USDA and the Department of Health and Human
                            Services (HHS). Each department contains agencies that contribute to
                            the national effort to assess, measure, and track STEC contamination
                            (see table 1).




                            Page 5                                   GAO-12-257 E. coli Contamination in Beef
Table 1: Agencies with Responsibilities Related to STEC Contamination in Beef

Department and agency                Responsibilities related to STEC contamination in beef
USDA
Food Safety and Inspection Service   Regulates the safety, wholesomeness, and proper labeling of domestic and imported meat
                                                                                        a
                                     under authority of the Federal Meat Inspection Act. Inspects slaughter plants, processing
                                     plants, and import establishments in the United States and can keep some products from
                                     entering the food supply via meat inspections at the plant level. May not mandate recalls of
                                     contaminated meat but does provide assistance and monitors voluntary recalls by the beef
                                     industry. Provides guidance to the beef industry regarding best practices for reducing STEC
                                     contamination.
Animal and Plant Health Inspection   Protects U.S. livestock and poultry from domestic and foreign diseases and pests under the
                                                                   b
Service (APHIS)                      Animal Health Protection Act. Reviews and approves applications for biological product
                                     licenses, such as vaccines, that could be used as part of a STEC preslaughter intervention.
                                     Manages the National Animal Health Monitoring System—a periodic, national survey of
                                     producers that focuses on management practices and animal health in feedlots.
Agricultural Research Service (ARS) Conducts research on a variety of STEC-related issues, such as prevention of STEC
                                    colonization in cattle, interventions to reduce STEC in beef, and STEC strain detection
                                    methods.
National Institute of Food and       Funds research on the prevention, detection, and colonization of STEC in cattle through
Agriculture (NIFA)                   grants to universities and other organizations.


HHS
FDA                                  Regulates the manufacture and distribution of food, food additives, and drugs for humans and
                                                                                               c
                                     animals under the Federal Food, Drug and Cosmetic Act. Ensures the safety and
                                     effectiveness of animal drugs, including those intended to reduce STEC prevalence in cattle,
                                     such as sodium chlorate.
CDC                                  Routinely gathers information from local and state health departments and laboratories and
                                     reports information about human STEC infections and the foods with which they are
                                     associated.
                                           Source: GAO.

                                           a
                                               21 U.S.C. §§ 601-683.
                                           b
                                               7 U.S.C. §§ 8301-8322.
                                           c
                                            21 U.S.C. §§ 301-399d.

                                           Several steps are involved in getting cattle from the farm to the consumer.
                                           Often, USDA and FDA provide regulatory oversight after the cattle leave
                                           the farm or feedlot and arrive at slaughter plants and food handling and
                                           manufacturing facilities. Figure 2 illustrates the beef production process
                                           from the farm to the consumer.




                                           Page 6                                            GAO-12-257 E. coli Contamination in Beef
Figure 2: Beef Production Process




In 2007, GAO designated federal oversight of food safety as a high-risk
area because of risks to the economy and to public health and safety. As
GAO has reported, the current fragmented system has caused
inconsistent oversight, ineffective coordination, and inefficient use of
resources. 2




2
 See most recently in GAO, Federal Food Safety Oversight: Food Safety Working Group
Is a Positive First Step but Governmentwide Planning Is Needed to Address
Fragmentation, GAO-11-289 (Washington, D.C.: Mar. 18, 2011).




Page 7                                        GAO-12-257 E. coli Contamination in Beef
                             USDA and university researchers identified several potential preslaughter
Several Interventions        interventions—including probiotics, sodium chlorate, and vaccines—that
Could Reduce STEC            could reduce STEC O157:H7 in cattle and, in some cases, may have
                             potential for reducing other strains of STEC. USDA conducts and funds
in Cattle                    research relevant to these interventions, including research on the
                             prevalence of STEC and on the interventions themselves.


Researchers Identified       Preslaughter interventions are treatments administered before cattle are
Preslaughter Interventions   slaughtered that can target STEC, usually the O157:H7 strain. Some
That Could Reduce STEC       interventions, such as sodium chlorate and vaccines, may also reduce
                             other pathogenic strains, but researchers have not conducted testing for
in Cattle                    the effects of interventions on other strains. According to representatives
                             for a beef industry group, most research on preslaughter interventions
                             has focused on those administered at the feedlots, although they may
                             also be administered in the holding pen of a slaughter plant. Preslaughter
                             interventions are not likely to eliminate STEC O157:H7 in cattle; instead,
                             the goal is to reduce the pathogen to levels that the HACCP systems at
                             slaughter plants are able to control effectively, according to beef industry
                             representatives and researchers. They also said that multiple
                             interventions are needed to accomplish this. Some studies suggest that a
                             few interventions are effective in reducing STEC O157:H7 in the digestive
                             systems or on the hides of cattle, but it may be difficult to demonstrate
                             that they reduce the levels of STEC O157:H7 in beef, according to
                             manufacturers of animal health products and researchers.

                             USDA and university researchers we spoke with identified several
                             potential preslaughter interventions for reducing STEC O157:H7 and, in
                             some cases, these interventions may have potential for reducing other
                             strains of STEC. Some of these interventions are in use for other
                             purposes, but few manufacturers have submitted applications for
                             preslaughter intervention products to target STEC—with the exception of
                             bacteriophages (viruses that infect and kill bacteria) and vaccines—
                             according to officials from USDA and FDA. The following are the
                             interventions that researchers identified, along with challenges for
                             bringing these interventions to market:

                             •   Antimicrobials. These are drugs used to treat infections by
                                 microorganisms, such as bacteria and viruses, and include synthetic
                                 and natural antibiotics. Antibiotics are currently used in cattle to treat
                                 or prevent diseases and increase growth. According to some
                                 researchers, it may not be feasible for industry to use antibiotics as a
                                 preslaughter intervention to reduce STEC because of concerns that


                             Page 8                                      GAO-12-257 E. coli Contamination in Beef
    such use will lead to greater prevalence of bacteria that are resistant
    to antibiotics. If resistant bacteria were to reach humans and cause
    illness, this illness might be more difficult to treat. Researchers also
    said that, for the same reason, it is unlikely that the veterinary
    pharmaceutical industry would pursue requesting approval for
    antibiotics as a preslaughter intervention. In April 1999, we reported
    that according to scientists, resistant strains of E. coli found in
    humans acquired resistance to antibiotics while in food animals. 3
    Resistant strains of E. coli may be transferred to humans through food
    or through contact with animals or animal waste.

•   Bacteriophages. These naturally occurring viruses infect bacteria and
    are highly specific—each type typically can kill a single strain or
    species of pathogenic bacteria. USDA, in consultation with FDA,
    licensed a mixture of bacteriophages that may be applied to cattle
    hides in holding pens at slaughter plants. Other bacteriophages,
    which could be administered orally, are at the experimental stage.
    According to researchers, it is possible for STEC O157:H7 to become
    resistant to some bacteriophages.

•   Colicins. These antimicrobial proteins are produced by certain STEC
    strains and can kill other strains. According to researchers, studies to
    date on the use of colicins to reduce STEC in cattle are few, and
    colicins are difficult to produce and expensive to use in studies.

•   Natural product extracts. These are compounds that are generally
    extracted from spices, aromatic herbs, fruits, and flowers, but can also
    be obtained from other natural products, such as marine plants. In
    particular, essential oils—a type of natural product extract—
    demonstrate antimicrobial activity that may reduce STEC O157:H7,
    according to researchers. Studies on the effect of essential oils on
    STEC O157:H7 in cattle are limited to the laboratory, but USDA and
    university researchers are developing field trials of citrus by-products,
    such as orange peel, which contain essential oils. Some compounds,
    or the products from which they are extracted, such as orange peel
    and brown seaweed extract, are currently used in cattle feed in some


3
 GAO, Food Safety: The Agricultural Use of Antibiotics and Its Implications for Human
Health, GAO/RCED-99-74 (Washington, D.C.: Apr. 28, 1999). For more information about
the use of antibiotics in animals, see GAO, Antibiotic Resistance: Agencies Have Made
Limited Progress Addressing Antibiotic Use in Animals, GAO-11-801 (Washington, D.C.:
Sept. 7, 2011).




Page 9                                         GAO-12-257 E. coli Contamination in Beef
    feedlots. Research is unclear on how much of the compounds or the
    products from which they are extracted, such as citrus and thyme oils,
    will pass through the cattle’s stomach, and it may be challenging to
    obtain a large quantity of these compounds to feed to cattle on a
    commercial basis, according to researchers.

•   Prebiotics. These nondigestible organic compounds can promote the
    growth and activity of beneficial bacteria in the digestive system of
    cattle, which in turn can reduce the prevalence of bacterial pathogens.
    According to USDA researchers, little work has been conducted on
    the effects of these compounds on STEC O157:H7 in cattle.
    Furthermore, the compounds may be expensive to use in cattle and
    may not pass through the cattle’s stomach.

•   Probiotics. These are live bacteria that can benefit the digestive
    system of cattle. According to USDA researchers, probiotics can
    prevent harmful colonization by bacteria by producing antibacterial
    compounds or by promoting healthy immune function. Researchers
    have conducted field trials to test whether varying amounts of certain
    probiotic strains reduce STEC O157:H7. Probiotics are widely used to
    increase weight gain. According to a few researchers, in order for
    probiotics to reduce STEC O157:H7, cattle may need to be fed large
    quantities, which may be costly to producers.

•   Sodium chlorate. This chemical kills STEC O157:H7 when it
    transforms to toxic chlorite inside the bacterial cell. This
    transformation occurs in both the stomach and the intestinal tract of
    cattle. According to representatives for a veterinary pharmaceutical
    manufacturer, the manufacturer is discussing with FDA applying for
    approval of sodium chlorate as an animal drug. According to a few
    researchers, it is likely that sodium chlorate would also reduce STEC
    non-O157.

•   Vaccines. These are biological preparations that alter the immune
    system to better fight specific pathogens. At least two manufacturers
    of animal health products have developed vaccines to target STEC
    O157:H7 in cattle and are seeking approval from APHIS to market
    them. One of these manufacturers received a conditional license for a
    vaccine in 2009 and, according to representatives from these
    manufacturers, applications for full licenses for two vaccines are




Page 10                                  GAO-12-257 E. coli Contamination in Beef
    pending. 4 According to a few researchers and representatives for a
    veterinary pharmaceutical manufacturer, administering higher doses
    of a vaccine would increase its efficacy but may be costly. For
    example, handling the cattle to specifically administer a STEC vaccine
    may increase labor costs. USDA officials also said that cattle
    producers may not directly benefit from administering these vaccines.
    Additionally, according to one university researcher and one animal
    health product manufacturing official, vaccines have the potential to
    reduce STEC non-O157, but a vaccine study of STEC non-O157 has
    not been conducted on animals. APHIS officials told us that they have
    not received information that could support this theory.

Table 2 provides a summary of preslaughter interventions, their approval
status, the agency responsible for their approval, and challenges for the
use of intervention.




4
  Conditional licenses are effective for a finite period, usually 1 year and may be renewed
at the discretion of APHIS. The data required for conditional licensure are reduced from
that needed for full licensure in that there needs only to be a “reasonable expectation” of
efficacy as defined by APHIS. Conditional licenses are not required prior to receiving a full
license but can be used to bring a product to market. For example, the conditional license
for the STEC O157:H7 vaccine allows cattle producers to use the vaccine under the
supervision of a veterinarian.




Page 11                                            GAO-12-257 E. coli Contamination in Beef
Table 2: Approval Status and Challenges for Preslaughter Interventions

                                Approved for use to                 Agency
                                reduce STEC O157:H7                 responsible
Preslaughter intervention       in cattle                           for approval                      Challenges for use of intervention
Antimicrobials                  No                                  FDA                               STEC O157:H7 may become resistant.
                                      a
Bacteriophages                  Yes                                 USDA                              STEC O157:H7 may become resistant.
                                                                    FDA
Colicins                        No                                  FDA                               Expensive and difficult to produce.
Natural product extracts        No                                  FDA                               May not pass the cattle’s stomach and may be
                                                                                                      difficult to obtain in large quantities.
Prebiotics                      No                                  FDA                               May be costly and may not pass the cattle’s
                                                                                                      stomach.
Probiotics                      No                                  FDA                               Cattle may need to be fed large amounts to
                                                                                                      reduce STEC.
                                                                                                              c
Sodium chlorate                 No                                  FDA                               None
                                      b
Vaccines                        Yes                                 USDA                              Cost associated with specifically administering a
                                                                                                      STEC vaccine.
                                          Source: GAO analysis of interviews with USDA officials, FDA officials, and university researchers.
                                          a
                                            USDA, in consultation with FDA, licensed a bacteriophage hide wash to be applied at the
                                          slaughterhouse prior to slaughter. Bacteriophages could also be administered orally, but FDA has not
                                          licensed any such product.
                                          b
                                              USDA granted conditional approval to one vaccine manufacturer.
                                          c
                                           Researchers we spoke with did not identify challenges when we asked them to discuss the
                                          challenges or roadblocks for each intervention. This does not mean that the intervention is without
                                          challenges, because there may be challenges that researchers are not aware of.

                                          USDA, the beef industry, and several researchers also identified
                                          preslaughter management practices that may affect STEC prevalence in
                                          cattle but that are not targeted to STEC. For example, basic sanitation
                                          practices—such as providing clean feed and water and keeping feedlots
                                          drained—have been identified by the beef industry and USDA as
                                          important steps in reducing the risk of STEC contamination in beef
                                          products. These practices are believed to be beneficial for the cattle’s
                                          health and welfare, although they have not been shown to be effective in
                                          reducing the pathogen, according to the beef industry and a USDA study.
                                          Researchers from one university noted interest in testing the effects of
                                          this and other preslaughter practices on STEC in cattle.

                                          Another preslaughter management practice researchers identified is diet
                                          modification, which includes modifying feed type, from feed grain to
                                          grasses, or the reverse; the frequency of feeding; and the quality of the
                                          grasses. Researchers have examined diet modification’s effect on the
                                          prevalence of STEC O157:H7 but have not reached a consensus about it.


                                          Page 12                                                                    GAO-12-257 E. coli Contamination in Beef
                      For example, some researchers have found that a diet with distillers
                      grains—a co-product of the production of ethanol from corn—increases
                      STEC O157:H7 prevalence in cattle, but others have found that it has no
                      effect. Furthermore, according to several USDA and university
                      researchers, diet modification may not be practical for reducing STEC
                      O157:H7 in cattle, partly because of the potentially high cost.


USDA Has Funded and   USDA has funded and conducted research on STEC prevalence in cattle,
Conducted Relevant    as well as research specific to preslaughter interventions. In fiscal years
Research              2009 and 2010, USDA’s NIFA, through its Agriculture and Food Research
                      Initiative, approved approximately $35 million in research grants related to
                      understanding and reducing STEC prevalence in cattle. NIFA provided a
                      total of about $28 million in five grants for research on how preslaughter
                      interventions may reduce STEC in cattle, a total of about $5 million in
                      three grants for research on how STEC behaves in the digestive system
                      of cattle, and about $2.5 million for one grant for research on both
                      preslaughter interventions and the behavior of STEC in the digestive
                      system of cattle.

                      In addition, USDA’s ARS has worked closely with other USDA agencies,
                      university researchers, and pharmaceutical manufacturers to research the
                      prevalence of STEC in cattle’s digestive systems and potential
                      preslaughter interventions, according to ARS officials. For example, these
                      officials said that ARS has conducted research on “super-shedders,”
                      which are cattle that appear to shed more STEC than other cattle in the
                      same herd. Regarding preslaughter interventions, ARS researchers have
                      investigated the effect of sodium chlorate on STEC in the digestive
                      system and, according to agency officials, ARS has collaborated with
                      companies to develop preslaughter interventions such as prebiotics,
                      bacteriophages, and sodium chlorate.




                      Page 13                                   GAO-12-257 E. coli Contamination in Beef
                     USDA’s APHIS exercises responsibility for licensing and regulating
USDA Exercises       animal biologic products that diagnose, prevent, manage, cure, or
Responsibility for   otherwise treat diseases of animals, including vaccines that can be used
                     as a preslaughter intervention. Industry representatives have identified at
Approving STEC       least two manufacturers of animal health products that have each
Vaccines, but Its    submitted an application to APHIS for approval of a STEC vaccine to treat
Approval             the O157:H7 strain in cattle, and USDA announced the approval of a
                     conditional license for one of these manufacturers.
Requirements Are
Unclear              According to representatives from two manufacturers of animal health
                     products that sought a license for STEC O157:H7 vaccines, it was
                     unclear whether FDA or USDA was responsible for reviewing and
                     approving their applications when they wanted to apply in 2001 and 2003.
                     It took more than a year before APHIS accepted their applications for
                     review, in part because of lack of clarity over whether FDA or APHIS
                     should be responsible for approving such vaccines, according to these
                     representatives. Specifically, APHIS is responsible for regulating vaccines
                     that diagnose, prevent, manage, cure, or otherwise treat diseases of
                     animals, but APHIS officials told us that because STEC O157:H7 does
                     not harm cattle, the agency had found prior to 2005 that regulatory
                     jurisdiction for STEC O157:H7 vaccines resided with FDA as a food
                     safety issue. According to these officials, the manufacturers of animal
                     health products told them that the licensing process would be clearer
                     under APHIS because it had more experience regulating conventional
                     veterinary vaccines than FDA.

                     In 2005, APHIS stated its policy on animal vaccines in a directive
                     explaining that it was responsible for regulating biological products such
                     as the STEC O157:H7 vaccine. 5 Specifically, the directive stated that
                     APHIS had the authority to approve products that claim to reduce
                     colonization or shedding of organisms that may not cause significant
                     clinical disease in animals but have the potential to cause the animal to
                     be a disease carrier. According to an FDA official, if a manufacturer
                     contacts FDA’s Office of New Animal Drug Evaluation seeking a license
                     for a STEC O157:H7 vaccine product, this office assists APHIS by
                     immediately directing the manufacturer to APHIS. The APHIS directive
                     expired as guidance in 2006, but because APHIS has not issued any



                     5
                      Animal and Plant Health Inspection Service, USDA, Center for Veterinary Biologics
                     Notice No. 05-07 (Mar. 4, 2005).




                     Page 14                                         GAO-12-257 E. coli Contamination in Beef
subsequent statements on this policy, an APHIS official said that the
policy in the directive remains in effect. This 2005 directive clarified
APHIS’s approval authority and role concerning vaccine approvals, but
APHIS’s approval requirements for STEC vaccines are not clear,
according to industry representatives.

APHIS officials said that they direct potential applicants for STEC vaccine
licensing to both the agency’s general guidance on demonstrating the
safety and efficacy of biological products and to its 2005 directive. 6
According to an APHIS official, the STEC vaccine is one of the most
difficult vaccines for which to show definitive, consistent, and reproducible
efficacy results. However, APHIS’s general guidance does not address
this and other unique challenges faced by manufacturers of animal health
products seeking STEC vaccine approval. For example, APHIS officials
said that a STEC vaccine manufacturer may need to demonstrate that its
vaccine is effective in a field setting—such as a feedlot in which cattle can
be naturally exposed to pathogens—if studies conducted in the laboratory
in which cattle are intentionally exposed to pathogens are insufficient to
demonstrate efficacy. With other vaccines, a laboratory study is often
sufficient because it can demonstrate consistent efficacy. However,
information on when laboratory and field studies are required to
demonstrate efficacy is not documented in the general guidance or 2005
directive. In contrast, the Canadian Centre for Veterinary Biologics
provides more specific guidance about when it requires the use of
laboratory or field studies to demonstrate efficacy for vaccine license
applications. In addition, neither the 2005 directive nor APHIS’s general
guidance provides clear, specific instruction to manufacturers on the
application process for STEC vaccines. For example, the 2005 directive
states that the vaccine products will be required to show “clinically
relevant efficacy as defined by APHIS” but does not explain what such
efficacy means. According to an APHIS official, “clinically relevant
efficacy” is the expectation that the vaccine’s efficacy is measurable,
reproducible, consistent, and shows a long-term effect in reducing the
disease in the animal, but this clarification is not specified in written
guidance. Guidance that does not give manufacturers the information
they need to submit an acceptable application could delay the approval




6
 APHIS’s general guidance includes Veterinary Services Memorandum No. 800.202 and
No. 800.204.




Page 15                                      GAO-12-257 E. coli Contamination in Beef
                       process even with the clarification on APHIS’s role concerning vaccine
                       approvals.

                       More specific guidance on the vaccine approval requirements may be
                       especially important to manufacturers of animal health products working
                       on STEC because of the challenges they face in demonstrating the
                       efficacy of targeted preslaughter interventions. This difficulty is due to
                       several biological factors specific to STEC, according to USDA officials,
                       industry representatives, and university researchers. First, the prevalence
                       of STEC is highly variable. For example, researchers said that STEC can
                       be absent from cattle—or present only at low levels—during a field trial at
                       a feedlot. That is, both treated and untreated cattle can have little or no
                       detectable STEC, and thus it can be difficult for researchers to
                       demonstrate that treated cattle have significantly lower levels of the
                       pathogen. Second, many factors—such as weather, the time of year, and
                       the cleanliness of the cattle’s hide—may affect the level of pathogenic
                       STEC in cattle, making it difficult to isolate the effects of an intervention.
                       Third, unlike other pathogens, STEC causes no visible symptoms in
                       animals, so detection requires testing for the presence of the pathogen
                       rather than just observation of the cattle.

                       APHIS officials said that APHIS does not have specific guidance on
                       STEC vaccines because it typically does not release such guidance for a
                       particular biological product until it has reviewed and approved three
                       applications, which gives the agency sufficient information to provide
                       specific guidance. They said that the agency’s general vaccine guidance
                       offers it flexibility during the application review process by not being too
                       prescriptive on requirements. During the course of our study, APHIS
                       addressed some of the concerns we raised by releasing a one-page
                       summary on licensing of preslaughter vaccines for a public meeting on
                       food safety, but it still does not have documented guidance on the
                       application process, including requirements specifically for these
                       vaccines.


                       USDA determined that six additional STEC non-O157 strains were
USDA Determined        adulterants in beef in September 2011, has developed a method to test
That Six Additional    for them in beef, and plans to use this method starting in June 2012.
                       Commercial tests are also available, and a few companies are voluntarily
STEC Strains Were      testing for these strains.
Adulterants and Has
Tests to Detect Them

                       Page 16                                    GAO-12-257 E. coli Contamination in Beef
USDA Determined That        In September 2011, USDA’s FSIS announced that it determined that six
Six Additional Strains      pathogenic strains of STEC—O26, O45, O103, O111, O121, and O145—
Were Adulterants and Has    were adulterants in raw ground beef and beef trim (the meat left over after
                            steaks and roasts are carved from a side of beef), in addition to STEC
Tests to Detect Them, but   O157:H7. According to CDC, at least 150 STEC non-O157 strains have
It Can Be Difficult to      been associated with illness, but the majority of those illnesses have been
Confirm Positive Results    traced to these six STEC non-O157 strains. There are several
                            consequences to these strains being adulterants, including the following:

                            •   Sale of beef contaminated with these strains is prohibited.

                            •   Beef slaughter and processing plants must have a HACCP plan in
                                place to identify and control the strains and to verify that the methods
                                used to control the strains are working properly. Verification could
                                include testing, but testing is not mandatory.

                            •   FSIS has more reason to routinely test a subset of products for these
                                strains and to request a recall for products deemed to be adulterated.

                            According to a September 20, 2011, notice in the Federal Register, 7 FSIS
                            intended to begin testing for these six strains in samples of raw ground
                            beef and beef trim at slaughter and processing plants in March 2012,
                            after it has reviewed comments from the public. Subsequent to this
                            notice, FSIS moved its test date to June 4, 2012. In conducting these
                            tests, FSIS plans to use a method developed by USDA’s ARS that was
                            first published in October 2010 and revised in November 2011. This
                            method has two key phases: (1) preliminary testing, which may take up to
                            2 days, and (2) isolation and confirmation, which may take an additional 2
                            to 4 days. These two phases are also used for STEC O157:H7 testing.

                            Preliminary testing involves two main steps. First, beef samples are
                            tested for two genes—known as stx and eae—that are known to make
                            E. coli pathogenic. Second, the samples are tested for other genes that
                            are specific to each of the six STEC non-O157 strains. Positive results in
                            both steps are considered a “potential positive,” which means the
                            pathogen may be present. According to an ARS official, if used as
                            planned, preliminary tests for the six strains are reliable. However, it is
                            possible that these genes are present in a beef sample but come from



                            7
                            76 Fed. Reg. 58,157 (Sept. 20, 2011).




                            Page 17                                   GAO-12-257 E. coli Contamination in Beef
different strains of bacteria. It is, therefore, necessary to isolate the
suspect strain and confirm that it is the source of the two genes that make
E. coli pathogenic.

Several steps are involved in the isolation and confirmation phase; two of
these steps may be difficult and time-consuming, according to ARS
officials. The first involves separating the suspected strain of pathogenic
E. coli from other bacteria using immunomagnetic separation beads that
contain antibodies (components of the human immune system) that
adhere to a specific strain of E. coli. According to an ARS official, it would
be very difficult to isolate the target strain without the use of these beads.
However, the official also said that the beads are not commercially
available for two of the six strains—O45 and O121. ARS currently buys
beads from a commercial supplier for the other four strains but has to
make them for O45 and O121, which is a time-consuming and costly
process, according to an ARS official. FSIS is currently searching for
companies willing to produce beads for the two strains and make them
commercially available and, according to an FSIS official, expects to have
test manufacturers in place by June 2012.

The second step involves growing the target strain by placing the
immunomagnetic beads onto a solid growth medium containing a mix of
nutrients that is specific to this strain and suppresses the growth of other
bacteria. According to an ARS official, scientists allow the bacteria
sticking to the beads to grow and multiply on the medium, using methods
that ensure the bacteria form colonies that are all from the same strain.
This makes it easier to identify the target strain and confirm that it has the
two disease-causing genes—stx and eae. However, according to the
ARS official, some of the six STEC non-O157 strains may not always
grow well on the medium that FSIS is currently using. If the strains do not
grow well, it will be difficult to confirm potentially positive results and,
consequently, beef samples that contain one of the six pathogenic strains
could incorrectly test negative. According to the ARS official, a revised
November 2011 testing method includes an improved growth medium for
the six strains. This official added that ARS has conducted various tests
to find the optimal growth medium for the six strains, and the medium
FSIS is using is the best currently available. Research is ongoing by ARS
and in the broader scientific community to develop a better growth
medium, according to this ARS official, and ARS will evaluate other
mediums as they become commercially available. See figure 3 for a
summary of the testing process.




Page 18                                    GAO-12-257 E. coli Contamination in Beef
Figure 3: Preliminary and Isolation and Confirmation Testing Phases for the Six STEC Non-O157 Strains




                                        Note: This figure shows the two main phases for E. coli detection testing. For a comprehensive
                                        description of all of the detection testing steps, see USDA’s Microbiology Laboratory Guidebook MLG
                                        5B.01.


Commercial Tests Are                    Preliminary tests to detect the six strains are commercially available, and
Available and Some                      at least one test manufacturer sells these tests for all six strains. ARS
Companies Are Testing                   collaborated with this manufacturer to develop the tests and is now
                                        collaborating with other manufacturers, many of which became interested
                                        in developing tests after USDA’s announcement that it had determined to
                                        consider the six strains as adulterants, according to an ARS official. A
                                        representative from one test manufacturer told us he was confident that
                                        his company could produce enough tests to meet the demand of the U.S.
                                        beef industry. Similarly, a representative from a second manufacturer told
                                        us that it is preparing to meet the demand.

                                        Starting on June 4, 2012, FSIS will expect slaughter and processing
                                        plants to have a plan in place to identify and control the six STEC non-
                                        O157 strains. Such a plan may include information on how the plant will
                                        use testing to verify that food safety systems are working properly. FSIS
                                        officials estimate that about 20 percent of U.S. slaughter plants are
                                        currently testing for STEC non-O157 strains, although FSIS did not know
                                        for which specific strains these plants are testing. Representatives from
                                        two beef processing plants—one of which is also a retailer—told us that
                                        they are testing for all six strains. The plant that is also a retailer will also
                                        require its beef suppliers to test for these strains before it accepts the
                                        beef. The retailer will also test for STEC O104, an additional STEC non-
                                        O157 strain, as soon as a test is commercially available for beef. The



                                        Page 19                                                GAO-12-257 E. coli Contamination in Beef
                       representative from this retailer did not report challenges with using the
                       commercially available preliminary test for the six strains. However,
                       commercial preliminary tests for the six strains are new, and according to
                       representatives from a test manufacturer, the manufacturer recently
                       started conducting field trials on the tests.

                       Both beef processing plants said they also carry out confirmation tests for
                       potential positive results through a third-party laboratory. An official from
                       one of these plants told us that he has not observed any difficulty in
                       growing the six strains after separation using the commercially available
                       growth mediums, but he noted confirmation of potentially positive results
                       for the six pathogenic strains can be a time-consuming process.
                       According to a test manufacturer representative, confirmation of
                       potentially positive results will likely be difficult for the beef industry, for
                       the same reasons it is proving difficult for FSIS.

                       If a plant detects one of the six strains in ground beef or beef trim, its
                       response is generally dictated by FSIS requirements. Possible responses
                       to a positive test include disposing of the beef or cooking it to kill bacteria.


                       Several researchers, U.S. agency officials, and a foreign government
Some Countries Have    official said that the United States is the leader in researching and
Practices That Could   employing preslaughter interventions. USDA officials, however,
                       commented that they would consider preslaughter practices other
Be Relevant to U.S.    countries have conducted if they are relevant to U.S. efforts to reduce
Efforts to Reduce      STEC in cattle. The following are some practices other countries have
STEC in Cattle         employed that may help reduce STEC in cattle and that are not currently
                       used in the United States:

                       Cattle cleanliness inspections. Several foreign governments conduct
                       cleanliness inspections that may reduce STEC in beef. For example,
                       European Parliament and the Council of the European Union regulations,
                       referenced by European Commission officials, require that (1) farmers
                       take adequate measures to ensure the cleanliness of cattle going to
                       slaughter, (2) operators of slaughter plants ensure cattle are clean before
                       accepting them, and (3) meat inspectors verify that the cattle about to be
                       slaughtered are clean. In the United Kingdom, meat inspectors use a five-
                       category rating system for cattle cleanliness that ranges from “clean and
                       dry” to “filthy and wet,” according to a 2002 guidance document from the
                       Food Standards Agency. Only cattle rated in the two highest categories
                       for cleanliness may proceed to slaughter. In Australia, according to its
                       standard for the hygienic production and transportation of meat and meat


                       Page 20                                     GAO-12-257 E. coli Contamination in Beef
products for human consumption, an inspector must determine that cattle
are clean prior to slaughter. If they are not, they can be passed for
slaughter subject to conditions that ensure that they do not contaminate
other animals, carcasses, and carcass parts. According to New Zealand
government officials, their inspectors check for hide cleanliness to help
prevent meat contamination. In contrast, in the United States, FSIS
assesses the health of cattle prior to slaughter but does not inspect for
cleanliness.

Testing for STEC. At least 12 European Union member countries
collected and reported data on STEC in live cattle in 2009, according to a
2011 European Food Safety Authority and European Centre for Disease
Prevention and Control report. 8 Such data are important to identify the
main sources of infections. In countries such as Sweden and Denmark,
this testing is conducted regularly. For example, in Sweden, government
officials collect about 2,000 fecal samples every 3 years, according to an
official from Sweden’s National Veterinary Institute. These samples are
collected at geographically distributed slaughterhouses throughout
Sweden. Sweden tests for STEC O157:H7 and started to test 1,000 fecal
samples for STEC O26 in its 2011 study. In Denmark, the National Food
Institute collects fecal samples from approximately 200 bulls per year to
test for STEC O157:H7, according to an institute official. In the United
States, APHIS has conducted feedlot studies that involved testing for
STEC in live cattle, but this testing was voluntary and last conducted in
1999.

Testing cattle from specific farms in Sweden. When a person becomes ill
from E. coli in Sweden, Swedish government officials try to determine its
source by interviewing this person, according to an official from Sweden’s
National Food Administration. If this person is suspected of having been
in contact with cattle from a specific farm, cattle from this farm will be
sampled. If there is an E. coli strain match with that of the ill person, this
official said that Sweden’s Board of Agriculture would then recommend
that the cattle from this farm be slaughtered at a slower rate so that the
carcasses can be tested for STEC and heat-treated if found positive.
Although this is a recommendation, this official stated that its


8
 European Food Safety Authority, European Centre for Disease Prevention and Control;
The European Union Summary Report on Trends and Sources of Zoonoses, Zoonotic
Agents and Food-borne Outbreaks in 2009; EFSA Journal 2011 (Parma, Italy: Mar. 22,
2011).




Page 21                                        GAO-12-257 E. coli Contamination in Beef
                      slaughterhouses follow the board’s recommendations. According to this
                      official, since 1996, Sweden has had 52 cases of human illnesses from
                      STEC—46 from the O157:H7 strain, 2 from O26, 2 from O121, 1 from O8,
                      and 1 from O103. In the United States, STEC O157:H7 in beef can be
                      traced back to the beef supplier, but USDA officials said that they do not
                      trace the source of the pathogen back to the farm and thus cannot make
                      recommendations for special testing from specific farms.


                      Preslaughter interventions for cattle have the potential to help reduce
Conclusions           STEC-related illnesses, although they are unlikely to be able to eliminate
                      all pathogenic strains in cattle. USDA, the beef industry, and university
                      researchers have been working to develop these interventions. Few
                      manufacturers have submitted applications for preslaughter intervention
                      products to target STEC, but at least two have submitted applications for
                      STEC vaccines. However, the approval requirements are unclear. In
                      2005, USDA’s APHIS clarified its responsibility for vaccines, but it still has
                      not provided specific guidance on the information it needs to approve a
                      vaccine for STEC. Without guidance that gives manufacturers clear and
                      more specific information they need to submit an acceptable application,
                      the approval requirements for STEC vaccines could face delays and
                      thereby increase the risk to public health. In addition, some countries
                      have employed practices not currently used in the United States that
                      potentially can inform U.S. efforts for reducing STEC in cattle.


                      GAO recommends that the Secretary of Agriculture take the following two
Recommendations for   actions:
Executive Action
                      •   Direct the Administrator of APHIS to provide more specific public
                          guidance on the license approval requirements for STEC vaccines in
                          order to help improve clarity and reduce potential delays in the
                          application process for these vaccines.

                      •   Explore practices employed by other countries that are not currently
                          used in the United States for reducing STEC in cattle and consider
                          whether the identified practices can inform U.S. efforts.

                      We provided a copy of our draft report to the Departments of Agriculture
Agency Comments       and of Health and Human Services. In its written response, USDA
and Our Evaluation    generally agreed with the information in the draft report. USDA neither
                      agreed nor disagreed with our recommendation that it provide more



                      Page 22                                    GAO-12-257 E. coli Contamination in Beef
specific public guidance on the license approval requirements for STEC
vaccines. USDA’s APHIS acknowledged that additional public guidance
may be beneficial to applicants and stated that it is committed to providing
as much specific public guidance as possible. However, APHIS stated
that more specific requirements may discourage product development
efforts, and APHIS does not release specific guidance about a new
product until it has reviewed and approved at least three applications.
Further, according to industry representatives, APHIS’s approval
requirements for STEC vaccines are not clear. Our recommendation is
intended to help improve clarity and reduce potential delays in the
application process for STEC vaccines. As stated in our report, we found
that guidance that does not give manufacturers the information they need
to submit an acceptable application could delay the approval process. We
also provided examples of areas in which more specific guidance, such
as clarifying the term “clinically relevant efficacy,” could reduce confusion.
APHIS addressed some of the concerns we raised by releasing a one-
page summary on licensing of preslaughter vaccines for a public meeting,
but this is not documented as guidance. We encourage APHIS to provide
more specific guidance that can reduce confusion without discouraging
product development of STEC vaccines. USDA agreed with our
recommendation to explore practices that are currently not used in the
United States for reducing STEC in cattle and consider whether the
identified practices can inform U.S. efforts. USDA’s letter is presented in
appendix II. The Department of Health and Human Services did not
comment on the draft report but provided technical comments. As
appropriate, we incorporated these technical comments and those
provided by USDA.


This report is intended for use by USDA management. We are sending
copies of this report to the appropriate congressional committees and
members, the Secretary of Health and Human Services, and other
interested parties. In addition, this report is available at no charge on the
GAO website at http://www.gao.gov.




Page 23                                    GAO-12-257 E. coli Contamination in Beef
We acknowledge and appreciate the cooperation and assistance
provided by USDA management and staff during our audit. If you have
questions about this report, please contact me at (202) 512-3841 or
shamesl@gao.gov. Contact points for our Offices of Congressional
Relations and Public Affairs may be found on the last page of this report.
GAO staff who made key contributions to this report are listed in
appendix III.

Sincerely yours,




Lisa Shames
Director, Natural Resources and Environment




Page 24                                  GAO-12-257 E. coli Contamination in Beef
Appendix I: Objectives, Scope, and
Methodology

              Our objectives were to determine (1) preslaughter interventions that may
              help reduce Shiga toxin-producing Escherichia coli (STEC) in cattle; (2)
              the U.S. Department of Agriculture’s (USDA) role in approving STEC
              vaccines; (3) the extent to which STEC strains have been determined to
              be adulterants in beef and the status of tests to detect them; and (4)
              practices, if any, other countries have employed that could reduce STEC
              in cattle and may be relevant to U.S. efforts.

              For all four objectives, we visited several cattle feedlots and a cattle
              slaughter plant in Colorado, which we selected because it is one of the
              largest beef-producing states. While in Colorado, we also interviewed
              USDA officials, beef industry representatives, and university researchers.
              In addition, in a nonprobability sample, we conducted a total of 71
              interviews with USDA, Centers for Disease Control and Prevention
              (CDC), and Food and Drug Administration (FDA) officials; foreign
              government officials; beef industry representatives; manufacturers of
              animal health products; federal and university researchers; and consumer
              group representatives with expertise in STEC in cattle. Our questions
              included descriptions of preslaughter interventions, roles of federal
              government in preslaughter interventions, and practices other countries
              have employed to reduce STEC in cattle that may be relevant to U.S.
              efforts. Because this was a nonprobability sample, the results cannot be
              generalized to the entire United States, but they can provide examples of
              research conducted on preslaughter interventions.

              To determine the preslaughter interventions that may help reduce STEC
              in cattle, we reviewed USDA and academic studies on preslaughter
              interventions, reviewed USDA documents on funding for STEC research,
              and met with USDA and university researchers and beef and
              pharmaceutical industry representatives. We identified these studies
              through interviews with USDA and university researchers.

              To determine USDA’s role in approving STEC vaccines, we reviewed
              USDA guidance, and interviewed USDA officials, manufacturers of animal
              health products, and university researchers.

              To determine the extent to which STEC strains have been determined to
              be adulterants in beef and the status of tests to detect them, we reviewed
              USDA documents on STEC detection tests and interviewed FDA and
              USDA officials, beef industry representatives, and detection test
              manufacturers.




              Page 25                                  GAO-12-257 E. coli Contamination in Beef
To determine practices, if any, other countries have employed that could
reduce STEC in cattle and may be relevant to U.S. efforts, we interviewed
CDC, FDA, and USDA officials; beef industry representatives; university
researchers; and consumer group representatives to determine if they
were aware of any such practices. We also reviewed international
studies, guidance, and requirements for food safety in beef and
interviewed international food safety officials. We did not independently
verify statements of foreign law.

We conducted this performance audit from January 2011 to March 2012
in accordance with generally accepted government auditing standards.
Those standards require that we plan and perform the audit to obtain
sufficient, appropriate evidence to provide a reasonable basis for our
findings and conclusions based on our audit objectives. We believe that
the evidence obtained provides a reasonable basis for our findings and
conclusions based on our audit objectives.




Page 26                                 GAO-12-257 E. coli Contamination in Beef
Appendix II: Comments from the U. S.
              Appendix II: Comments from the U. S.
              Department of Agriculture



Department of Agriculture




              Page 27                                GAO-12-257 E. coli Contamination in Beef
Appendix II: Comments from the U. S.
Department of Agriculture




Page 28                                GAO-12-257 E. coli Contamination in Beef
Appendix III: GAO Contact and Staff
                  Appendix III: GAO Contact and Staff
                  Acknowledgments



Acknowledgments

                  Lisa Shames, (202) 512-3841, or shamesl@gao.gov
GAO Contact
                  In addition to the individual named above, Thomas Cook, Assistant
Staff             Director; Kevin Bray; Mark Braza; Christina E. Bruff; Allen T. Chan;
Acknowledgments   Barbara El Osta; Brenda Muñoz; Katherine M. Raheb; Sushil Sharma;
                  Benjamin Shouse; Carol Herrnstadt Shulman; and Kiki Theodoropolous
                  made key contributions to this report.




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                  Page 29                               GAO-12-257 E. coli Contamination in Beef
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