V Vol. 22, No.
9 September 2000
CE Refereed Peer Review
FOCAL POINT
★Food animal producers and
veterinarians share an interest in
supplying packers with residue-
free animals to maintain
consumer and government
confidence in the safety of food
supplies.
KEY FACTS
■ Food animal producers and
veterinarians need to assume
responsibility for food safety.
■ Violative tissue residues of
chemicals, antimicrobials, and
other potential contaminants are
a public health concern and the
object of a national monitoring
and surveillance program.
■ The education of anyone using
animal health care products is a
key to preventing violative tissue
residues in meat, milk, and eggs.
■ Hazard analysis and critical
control point plans followed by
packers must address chemical
hazards, such as violative tissue
residues of animal health care
products and other potential
contaminants.
Food Safety:
Antimicrobial Residues
National Pork Producers Council
Des Moines, Iowa
Paul Sundberg, DVM, PhD
ABSTRACT: Animal health products are management tools used by food animal producers
and veterinarians to provide for their animals’ health and welfare. These products can also
help to minimize production costs and economically enhance production performance. To en-
sure public health, regulatory bodies have developed methods of determining the maximum
concentration of compounds and chemical residues that are permissible in the food supply. In
the United States, the National Residue Program samples and tests the nation’s production of
meat, poultry, and eggs to ensure that these limits are not violated. Commodity organizations
have developed quality-assurance programs on the safe use of animal health products. These
programs serve as an on-farm precursor of the packer’s hazard analysis and critical control
point plans addressing residue avoidance.
F
or the food animal production industry to be successful and continue to
grow, producers need to continually improve their ability to provide cus-
tomers with safe products. Meat quality may vary according to various la-
bels determined by consumers, such as tenderness, taste, or color. However,
meat safety is legally determined by whether products comply with chemical and
antimicrobial residue limits. Without a basic assurance of food safety, consumers
lose confidence in the safety of food products.
MAXIMUM RESIDUE LIMIT
Residue is any compound present in edible or target tissues of an animal, ei-
ther from intentional or inadvertent introduction of the compound to the ani-
mal. Residue includes the compound itself, its metabolite, and other substances
that form in or on food after introduction of the compound.1 The maximum
residue limit (MRL) is the maximum concentration of a substance allowed in a
particular tissue or commodity (e.g., meat, milk, or eggs).
Historically, MRLs have been set using toxicologic research that provides a bi-
ologic no-observable-effect-level (NOEL) for each compound. The NOEL is
used to mathematically determine an acceptable daily intake (ADI) for the com-
pound. The ADI then serves as a basis for calculating the MRL in meat, milk,
and eggs in such a manner that the ADI (using estimated daily human food in-
take of all these commodities) is not exceeded.2 In 1996, the U.S. FDA pub-
lished a guideline for the microbiologic testing of antimicrobial drug residues in
food: The agency considers safe to be that level of antimicrobial residues in food
Compendium September 2000
with no meaningful effect on the intestinal microflora
of consumers.3 This guideline has led to an effort to
evaluate in vitro and in vivo model systems that could
be used to establish new ADIs and MRLs for some an-
timicrobial drug residues in foods.
The Codex Alimentarius Commission, established in
1962, is the joint food standards program of the Food
and Agriculture Organization (FAO) and the World
Health Organization (WHO), both programs of the
United Nations. The commission was established to
help protect the health of consumers and facilitate fair
trade by establishing international food standards,
codes of practices, and other guidelines.4 Once they
were developed, Codex standards (which include an
MRL for particular veterinary drugs) are recommended
to national governments by the FAO and WHO. Be-
cause these organizations cannot make appropriate
rule- or law-making decisions, a Codex standard is not
enforceable in a nation if it is not adopted by that na-
tion. Although a country can establish its own MRL for
a compound, if that MRL differs from the Codex stan-
dard with the intent of acting as a nontariff trade barri-
er and therefore cannot be scientifically defensible, the
action may be brought before the World Trade Organi-
zation if the disputing countries are members.
Therefore, despite attempts to harmonize food safety
standards, the possibility of country-specific MRLs ex-
ists and can lead to confusion during international trad-
ing. For example, country A may set a withdrawal on a
product or compound with the intent of complying
with its particular MRL for that product in meat.
Country B may have a lower, more stringent MRL on
the same product in meat (perhaps even zero tolerance),
which would mean the product would either have a
longer withdrawal time or perhaps a prohibition on use.
Thus even though the producers of country A follow
their product’s labeled directions, their meat products
may be condemned in country B for violating that
country’s MRL. International standards agreed on by
the Codex Alimentarius Commission have helped re-
solve some of these problems; however, the demands of
the growing global market require additional standards.
In the United States, three federal government agen-
cies share responsibility for the regulation of pesticides,
antimicrobials, and other chemicals used during food
animal production. The Environmental Protection
Agency approves the use of pesticides and sets toler-
ances if the use of that pesticide may result in residues
in or on food.5 The FDA sets residue limits for animal
drugs and environmental contaminants and enforces
these and pesticide tolerances in domestically produced
or imported foods that may be shipped in interstate
commerce. The U.S. Department of Agriculture (USDA)
MAXIMUM RESIDUE LIMITS ■ MULTICOMPONENT TESTING PROGRAM ■ MONITORING AND SURVEILLANCE
Food Animal
Food Safety Inspection Service (FSIS) is responsible for
ensuring that USDA-inspected meat and poultry prod-
ucts are safe, wholesome, and free of adulterating resi-
dues and are accurately labeled.6
NATIONAL RESIDUE PROGRAM
The USDA FSIS National Residue Program (NRP)
is a multicomponent analytic testing program for
residues in domestic and imported meat, poultry, and
egg products. The program uses a variety of sampling
plans to verify that slaughter establishments are fulfill-
ing their responsibilities in preventing violative residues
and develops national data on chemical residues to sup-
port risk assessment, enforcement, and educational
activities. The range of chemical compounds is com-
prehensive in scope and includes approved and unap-
proved pharmaceutical drugs and pesticides known or
suspected to be present in food animals in the United
States and in countries exporting products to this coun-
try.7
Because thousands of chemicals and compounds
worldwide are used in food animal production, it is im-
practical if not impossible for the FSIS to test for every
one. Each year, an agency surveillance advisory team
convenes to identify and discuss compounds of poten-
tial public health concern. An interagency residue pri-
oritization committee then meets to allocate resources
to test for compounds that are of greatest concern and
to develop a statistically based residue monitoring plan
that provides defined levels of assurance of detecting
residue violations in meat, poultry, and eggs.7 Thus the
list of prioritized compounds of concern is updated and
may change on at least an annual basis.
Although special projects are possible, NRP plant
procedures can be divided into two activities: monitor-
ing and surveillance. Monitoring information is ob-
tained through a statistically based random selection of
specimens of normal-appearing tissue from inspection-
passed carcasses (healthy animals). Generally, for a spe-
cific slaughter class or compound pair, the number of
randomly chosen specimens (300) provides a 95%
probability of detecting at least one violation when 1%
of the animal population is violative.8
Surveillance or enforcement testing consists of the
analysis of specimens obtained from individual animals
or lots based on clinical signs, herd history, or post-
mortem findings. This testing detects individual ani-
mals with violative tissue residue, is emphasized in high
prevalence populations, and may also be used to follow
up on producers who have had previous residue viola-
tions when marketing animals. The testing frequency is
based on decisions by program employees using region-
al guidelines or direct observations.8
Food Animal
In-Plant Screening Tests
■ SOS (Sulfa-On-Site): This test is used in
approximately 50 of the largest swine-
slaughtering facilities to check swine urine for
sulfonamide residues.
■ CAST (Calf Antibiotic and Sulfonamide Test):
This tissue microbial inhibition test is used on
veal calves weighing less than 150 pounds or
younger than 3 weeks of age. Cultures with
inhibition zones greater than 18 mm are sent
to a laboratory for confirmation.
■ STOP (Swab Test On Premises): This
microbial inhibition test is used on kidney
tissue to detect antibiotics and sulfonamides.
■ FAST (Fast Antimicrobial Screen Test): A
faster replacement of the CAST and STOP
tests, it screens kidney and liver tissue in
virtually all the larger bovine-slaughtering
plants.
IN-PLANT TESTS
Rapid screening tests are used in packing plants to
detect the presence of antimicrobial residue. Because
they are screening tests only, laboratory confirmation of
violations is required. USDA FSIS confirms samples
that test positive by using a bioassay procedure for an-
tibiotic residue detection and quantification9 (see In-
Plant Screening Tests).
Compounds tested during 1997 (the most current
year for which statistics have been compiled and pub-
lished) included antibiotics (chlortetracycline, ery-
thromycin, gentamicin, neomycin, oxytetracycline,
penicillin, streptomycin, tetracycline, and tylosin), sul-
fonamides (sulfachlorpyridazine, sulfadimethoxine, sul-
famethazine, and sulfathiozole), arsenicals, chlorinated
hydrocarbons and chlorinated organophosphates, halo-
fuginone, ivermectin, carbadox, and clenbuterol. The
results are reported in the FSIS Domestic Residue Data
Book by compound for each class of animal. Of the
26,626 total monitoring analyses made, 72 showed vi-
olative concentrations of residues (20 sulfonamides, 32
antibiotics, 9 chlorinated hydrocarbons and chlorinated
organophosphates, 6 ivermectin, and 5 arsenic).8
RESIDUE AVOIDANCE
The goal of residue avoidance is not necessarily the
absence of residues. Rather, it is the avoidance of viola-
BIOASSAY PROCEDURES ■ ACCEPTABLE RESIDUE LEVELS ■ INSPECTION GUIDELINES
Compendium September 2000
Producers’ Responsibilities for
Animal Health Care Products
■ Identify and track animals to which drugs were
administered.
■ Maintain a system of medication and treatment
records that, at a minimum, identify the animal(s)
treated, date(s) of treatment, drug(s)
administered, who administered the drug(s),
amount administered, and withdrawal time
before slaughter.
■ Properly store, label, and keep an account of
all drug products and medicated feeds.
■ Obtain and use veterinary prescription drugs
only through a licensed veterinarian based on
a valid veterinarian–client–patient relationship.
■ Educate all employees and family members
involved in treating, hauling, and selling the
animals on proper administration techniques,
observance of withdrawal times, and methods
to avoid marketing adulterated products for
human food.
tive concentrations of residues, which may include total
absence. Some minute level of residue may be accept-
able if scientific data show there is no risk to consumers
through the food supply (i.e., residues below the MRL
for that compound). For example, in 1997 only 101
(1%) of 7732 monitoring samples from all slaughter
classes had nonviolative but detectable residues of an-
tibiotics.8 This concept is easily misunderstood by con-
sumers and is important to understand because of each
country’s right to set its own MRLs as long as they are
scientifically defensible and do not violate international
trading agreements.
By Food Animal Producers
In 1993, the FDA published its Compliance Policy
Guide (CPG), which provides regulatory guidance to
its inspectors for the development of cases resulting
from the use of animal drugs contrary to label direc-
tions and resulting in violative tissue residue concentra-
tions.10 CPG 7125.37, Proper Drug Use and Residue
Avoidance by Non-Veterinarians, outlines the producers’
responsibilities when using animal health care products
(see Producers’ Responsibilities for Animal Health Care
Products). Following these guidelines ensures that
food-producing animals are free of violative antimicro-
Compendium September 2000 Food Animal

bial and chemical residues and that they leave for the packing plant.
these animal health care prod-
10 Good Production Practices for These screening tests are general-
ucts will continue to be available Quality-Assured Pork Production ly available in multiple test kits
to the producer for use when that are economical enough to be
needed. Food Safety used for both spot-testing indi-
In 1996, the USDA published 1. Identify and track all treated animals. vidual shipments of animals and
the Final Rule on Pathogen Reduc- 2. Maintain medication and treatment periodic testing of animals and/
tion: Hazard Analysis and Critical records. or feeds to verify their compli-
Control Point (HACCP) Systems. 3. Properly store, label, and account for all ance with the production sys-
HACCP is designed to prevent drug products and medicated feed. tem’s plan for antimicrobial use
food safety problems resulting 4. Obtain and use veterinary prescription
and residue avoidance. Although
from microbial, chemical, or phys- these tests are useful for some an-
drugs only based on a valid
ical hazards in food instead of re- timicrobials, many of those used
lying on finding them after they veterinarian–client–patient relationship. in modern production systems
happen. Although HACCP does 5. Educate all employees and family do not have a specific ELISA-
not remove or diminish the regu- members on proper administration based on-farm test. Continuing
latory authority of the FSIS, it techniques and withdrawal times. research and product develop-
does increase the responsibility of 6. Use drug residue tests when appropriate. ment are needed to supply food
the packing plant to ensure that animal producers with economi-
their products are not adulterated Efficient Production of a Quality Product cal on-farm testing alternatives.
by the presence of residues above 7. Establish an efficient and effective herd
permitted levels when they enter health management plan.
By Food Animal
commerce. Because violative an- Practitioners
8. Provide proper swine care.
timicrobial and chemical residues Food animal veterinarians are
cannot be removed from the meat 9. Follow appropriate on-farm feed qualified to offer drug use and
once the animal is processed, pro- processing and commercial feed residue avoidance advice to pro-
ducers are responsible for supply- processor procedures. ducers. Thus practitioners serve
ing packers with animals that are 10. Complete the quality-assurance checklist as key educators in the com-
free from this HACCP-identified annually, and become recertified every modities’ quality-assurance pro-
hazard. 2 years. grams. Regardless of whether
Beef, veal, milk and dairy beef, they share legal responsibility for
and pork quality-assurance pro- residue avoidance from the ani-
grams involve good production and management prac- mal drugs they use, dispense, or prescribe, veterinarians
tices that serve as the on-farm precursor to the packers’ must maintain their professional knowledge of pharma-
residue avoidance HACCP plans. These programs are cology, anatomy, and physiology to be credible, expert
designed to provide the educational opportunity need- sources of information.
ed for producers to understand each of the CPG The Federal Food, Drug, and Cosmetic Act (FD&C
7125.37 points and implement them into their produc- Act) was amended in 1968 to create the mechanism for
tion systems. Although an individual commodity’s the approval of animal drugs. This amendment restrict-
quality-assurance program has specific practices that ed the use of animal drugs to only the species and usage
apply to their production systems, they each generally specified on the label. Strict interpretation of the
follow similar outlines to the Level III section of the FD&C Act, however, would have made it impossible to
National Pork Producers Council’s Pork Quality Assur- provide proper veterinary care in the food animal in-
ance Program and pork production’s 10 Good Produc- dustry.
tion Practices11 (see 10 Good Production Practices for The FDA recognized the dilemma for veterinarians
Quality-Assured Pork Production). They mimic the created by this 1968 amendment. Through two Com-
CPG 7125.37 and also offer a review of management pliance Policy Guides, the FDA adopted a policy of not
practices that help minimize antimicrobial use during ordinarily penalizing veterinarians who prescribe drugs
production. in an extralabel manner, providing the veterinarian
makes a professional judgment that the health of the
By On-Farm Testing animals to be treated is “immediately threatened and
Multiple companies offer ELISAs for on-farm testing suffering or death would result from failure to treat the
of the presence of antimicrobials in animals before affected animals.” In addition, criteria regarding diag-

QUALITY-ASSURANCE PROGRAMS ■ SPOT-TESTING SHIPMENTS ■ EXTRALABEL DRUG USE

Food Animal
nostic needs, product selection, animal identification,
and safe product use must be met.10
An important distinction needs to be made when it
comes to using products off-label (in a manner not de-
scribed on the label). Off-label use by producers on
their own initiative is illegal, and producers who do so
are subject to regulatory enforcement action by the
FDA. Extralabel use refers to the off-label recommen-
dations for use of a drug by a veterinarian under the
conditions described in the FDA policy guide and in
accordance with the Animal Medicinal Drug Use Clari-
fication Act (AMDUCA) of 1994. AMDUCA codified
the ability of herd veterinarians to use their professional
judgment and, when necessary, prescribe drugs in an
extralabel manner. However, for drugs administered in
the feed, there is no provision for extralabel uses by ei-
ther veterinarians or producers.
Extralabel use of drugs by food animal veterinarians
means that they accept additional responsibilities re-
garding the avoidance of violative tissue residues that
could result from that use. The AVMA published its
Extra-Label Drug Use Algorithm that helps practitioners
decide when extralabel use in food-producing animals
is permitted according to the AMDUCA regulations.12
Stipulations for such use include accepting added re-
sponsibility for food safety, establishing extended with-
drawal times, maintaining required records, and label-
ing the extralabel use drugs appropriately.
THE FUTURE
What the NRP of the future will look like because of
HACCP is yet to be determined. Additional responsi-
bilities borne by packers could mean additional respon-
sibilities transferred to producers and veterinarians.
Packer HACCP plans must address the chemical food
safety hazard of violative tissue residues. Because FSIS will
continue to conduct a comprehensive residue detection
program, there will be increased pressure on packing
plants to verify that their products are not adulterated by
residues because such a violation might be an indication
of an HACCP plan failure and could lead to regulatory
action against the plant (in addition to the animal suppli-
er). Repeated residue violations could indicate an HACCP
system failure that could result in suspension or with-
drawal of FSIS inspection.13 If that becomes the case,
packers might resort to any of several options for ensuring
that incoming animals do not bear violative residues13:
• Rejecting animals assessed to be at risk for having vi-
olative residues
• Specifying the management conditions necessary for
animals to be processed for human consumption
• Purchasing from producer-suppliers that have imple-
OFF-LABEL DRUG USE ■ DRUG-USE ALGORITHM ■ ECONOMIC IMPACT
Compendium September 2000
mented proper animal drug and pesticide use proce-
dures, which may include periodically visiting pro-
ducer-suppliers or requiring third-party verification
of implementation of the procedures
• Requiring written assurances from producer-suppli-
ers that all animals meet the plant’s contract specifi-
cations
• Periodically using analytical tissue residue tests to
verify that the supplier information is correct
Although each of these options has specific draw-
backs and caveats for packers, they also have the poten-
tial to impact the economic viability of producers. Dis-
cussions among government regulatory agencies,
packers, and food animal producers will need to ensure
that each understands their respective responsibilities
and the implications of their actions and policies. It is
imperative that producers and their veterinarians use
animal health products safely, according to labeled di-
rections unless indicated by the stipulations of AMDU-
CA, and only when needed so that packers can contin-
ue to have confidence that they are purchasing only
safe, residue-free animals.
REFERENCES
1. Domestic Residue Data Book—National Residue Program
1996. Washington, DC, USDA-FSIS, Office of Public Health
and Science, 1996.
2. Fernandez AH: Human Food Safety of Tetracyclines—Expert
Review. Washington, DC, HHS-FDA, Center for Veterinary
Medicine, 997.
3. Microbiological Testing of Antimicrobial Drug Residues in
Food, guideline #52, docket #93D–0398. Washington, DC,
HHS-FDA, 1996.
4. Codex Alimentarius Backgrounder. Washington, DC, USDA-
FSIS, Congressional and Public Affairs Staff, 1999.
5. Food and Drug Administration Pesticide Program—Residue
Monitoring 1998. Washington, DC, HHS-FDA, 1998.
6. Domestic Residue Data Book—National Residue Program
1996. Washington, DC, USDA-FSIS, Office of Public
Health and Science, 1996.
7. 1999 National Residue Program—Blue Book. Washington,
DC, USDA-FSIS, Office of Public Health and Science,
Chemistry and Toxicology Division, Emerging Issues
Branch, 1999.
8. Domestic Residue Data Book—National Residue Program
1997. Washington, DC, USDA-FSIS, Office of Public
Health and Science, 1997.
9. Microbiology Laboratory Guidebook, ed 3, vol 1 and 2. Wash-
ington, DC, USDA-FSIS, Office of Public Health and Sci-
ence, Microbiology Division, 1998.
10. Compliance Policy Guides. Washington, DC, HHS-FDA,
Public Health Service, Office of Regulatory Affairs, Office of
Enforcement, Division of Compliance, 1995.
Compendium September 2000
11. Pork Quality Assurance Program™. Des Moines, IA, Nation-
al Pork Producers Council, 1997.
12. Extralabel drug use (ELDU), AMDUCA guidance brochure.
JAVMA 212(4):suppl, 1998.
13. Stephan GE: How the residue monitoring program will
change. Proc 1998 Allen D. Leman Swine Conf:197–201, 1998.
Food Animal
About the Author
Dr. Sundberg is Assistant Vice President, Veterinary Is-
sues, National Pork Producers Council in Des Moines,
Iowa. He is a Diplomate of the American College of Vet-
erinary Preventive Medicine.