Testimony

on behalf of the

**National Cattlemen's Beef Association**

with regard to

Reviewing Advances in Animal Health Within the Livestock Industry

submitted to the

United States House of Representatives - Committee on Agriculture

Subcommittee on Livestock, Dairy, and Poultry

The Honorable Leonard Boswell, Chairman

submitted by

Dr. Mike Apley

September 25, 2008

Washington, DC

![](media/image1.jpeg){width="4.742361111111111in"
height="1.1631944444444444in"}

Chairman Boswell, Ranking Member Hayes, and Members of the Committee, my
name is Mike Apley. I am an associate professor of beef production
medicine, a clinical pharmacologist, and the Director of the PharmCATS
Bioanalytical Laboratory located at Kansas State University. I am also a
member of the National Cattlemen's Beef Association's (NCBA) Cattle
Health and Well Being Committee. I appreciate the opportunity to be here
today to talk about the use of drugs to prevent and treat disease within
the cattle industry.

Animal health and well-being are top priorities for cattle producers
across the country. Without healthy animals, we do not have a healthy
industry, so we utilize important tools like vaccines, antimicrobials,
and other drugs to control disease, treat disease, and provide a higher
quality of life for our cattle while keeping the food supply safe.
Ongoing activist and media reports, however, suggest that the use of
drugs in animal agriculture is often inappropriate and that the use of
drugs is poorly controlled. Misleading statements such as these have put
an undue spotlight on animal drugs and threatens to undermine the
science-based approval process we have for these products. One of the
most important pieces of information that should come out of today's
hearing is that consumers need to know that, by law, no meat sold in the
United States is allowed to contain drug residues that violate Food and
Drug Administration (FDA) standards. Additionally, all products approved
by FDA for use in food producing animals must first pass significant
human food safety benchmarks.

It is also important to recognize that animal drugs go through a
rigorous, science-based testing process before they are approved for
use. FDA, the U.S. Department of Agriculture (USDA), veterinarians,
animal health companies, producer organizations, and other stakeholders
have implemented several layers of human health protections during the
past decade to reduce any risks associated with antibiotic use in
animals.

FDA approves antibiotics and the specific dosage rates to treat specific
diseases or conditions, and producers are legally required to follow
these precise label directions. This rigorous approval process was made
more stringent in 2003 when FDA finalized an additional safety measure
requiring an antibiotic resistance risk assessment for all new and
existing antibiotics known as Guidance 152 (Guidance for Industry Part
152).

FDA's Center for Veterinary Medicine (CVM) is responsible for ensuring
that animal drugs are safe, effective, and manufactured to the highest
quality standards. The standards and processes for reviewing an
antibiotic used to treat animals is essentially the same as that for an
antibiotic used to treat humans, except for the fact that animal drugs
have to go through additional food safety assessments that human drugs
do not. Every drug is subject to a safety assessment, efficacy
assessment, and quality or manufacturing assessment before it is
approved.

The safety assessment layer of the approval process requires sponsors to
submit data showing use of the antibiotic is safe for the human or
animal in which it is to be used. The safety assessment for food animals
is more stringent than that for human antibiotics in three respects:

1.  While FDA conducts a risk-benefit assessment for human antibiotics
    in which it weighs benefits against risks, there is no consideration
    of benefits in the review of antibiotics used in food animals. This
    means any animal or human health risks for products under review
    must be extremely low since FDA does not consider any benefits to
    offset the risks.

2.  The safety assessment for food animal antibiotics requires sponsors
    to submit human food safety studies to ensure meat from animals
    treated with the antibiotic will be safe for human consumption. Data
    from these studies are used to establish withdrawal periods, or the
    amount of time prior to processing during which antibiotics cannot
    be used in order to ensure there are no residues above tolerance
    levels in the final food product.

3.  In 2003, FDA implemented an additional safety measure that "outlines
    a comprehensive, evidence-based approach to preventing antimicrobial
    resistance that may result from the use of antimicrobial drugs in
    animals." This risk assessment process was a priority action item in
    the U.S. Public Health Action Plan and is required for all newly
    proposed antibiotics. Significantly, CVM is working with animal
    health companies to also examine all existing, approved products
    using this new methodology.

Both the animal and human drug approval processes require efficacy
assessments. This means the submitting company must provide data from
geographically diverse, statistically-designed studies that show the
product will work in the way it is intended to provide a clinical
improvement or cure.

Finally, approval of animal and human drug products require a quality or
manufacturing assessment consisting of facility inspections, assurance
of product stability, adherence to good manufacturing practices and
other procedures to assure FDA the sponsor can manufacture the product
in the approved form.

In addition, USDA's Food Safety and Inspection Service (FSIS) conducts
tests to ensure withdrawal periods are being followed and beef products
entering the food supply do not contain antibiotic levels that violate
FDA standards. The testing protocol for the FSIS National Residue
Testing Program has been updated continuously since its inception in
1967.

Once the products have been approved, many are used to prevent animal
disease. There are some who will claim that the cattle industry is
dependent on drugs to fix the problems associated with our production
methods. While we prefer to prevent diseases, animal drugs are just one
tool we utilize to control disease. The cattle industry strives to
invent and improve production practices that help minimize the use of
drugs and prevent diseases.

An example of an advance in disease prevention management is the
increasing availability of "backgrounded" cattle which have received
appropriate immunizations for bovine respiratory disease and are then
held in local environments to overcome the stress of weaning prior to
being shipped to a feeding facility. These cattle are sold at a premium
due to their reputation for decreased disease occurrence at the feeding
facility.

Another example of management practices reducing the need for
therapeutic intervention is the "Sandhills Calving System". Named for
the intense cow/calf production area in the sandhills of Nebraska, this
system involves periodically moving cows which have not yet calved away
to new calving areas and leaving behind the cows and calves which have
recently calved. In this way any shedding of disease organisms and
related disease outbreaks are isolated within a subset of the animals
and prevented from spreading to the entire herd.

The importance of assuring adequate colostrum intake in newborn calves
has been demonstrated repeatedly, including data showing that inadequate
intake can result in differences in health performance as far removed as
in the feedlot phase of beef production. The economic incentive to pay
attention to colostrum intake is now based on more than just neonatal
health on the farm of origin in an industry where source identity of
cattle throughout the production cycle becomes more common place through
alliance programs, retained ownership, and branded beef programs.

Despite continually advancing management practices, vaccines remain a
staple of preventive programs in cattle. While there are vaccines with
demonstrated field efficacy for some pathogens related to bovine
respiratory disease, we still await vaccines with consistent, proven
efficacy for diseases such as systemic or enteric salmonellosis,
infectious pododermatitis (foot rot), *Mycoplasma bovis* involved in the
bovine respiratory disease complex, infectious bovine
keratoconjunctivitis (pinkeye), and anaplasmosis. It is crucial that
funding be provided for basic and applied research leading to increased
vaccine availability.

Once a disease has taken hold, we must utilize animal drugs to control
the disease and prevent its spread. Treatments for control of some
cattle diseases have been approved by FDA/CVM. For example, there are 5
antimicrobials approved for control of bovine respiratory disease. When
appropriate, these applications are very effective in decreasing
morbidity and death.

Another example of using antimicrobials to control disease is the
occurrence of clinical anaplasmosis in cattle. *Anaplasma marginale* is
a blood cell parasite that causes loss of red blood cells in cattle due
to infected cells being cleared from the body. In cattle less than one
year old, the clinical signs are mild due to the animal's ability to
regenerate red blood cells while mounting an immune response. As animals
age, the severity of the disease worsens to include death as a likely
outcome. Chlortetracycline may be fed to cattle at risk for the disease
during and immediately after the vector season to control clinical signs
while allowing infection that results in a carrier status and immunity
to the disease.

Anaplasmosis is a good example in examining the use of the term
"subtherapeutic." Chlortetracycline is effective for controlling the
effects of anaplasmosis. The approved in-feed dose for this application
is 0.5 to 2.0 mg/lb of body weight per day in beef and non-lactating
dairy cattle over 700 lbs, and 350 mg per animal per day in beef cattle
less than 700 lbs. In comparison, A dose of 10 mg/lb per day may be used
in the feed for treatment of bacterial pneumonia caused by *Pasteurella
multocida* organisms susceptible to chlortetracycline.

The point is that the term "subtherapeutic" is often interpreted to mean
"low concentrations" or "low dosage". In the case of anaplasmosis, a
relatively low dose of the antimicrobial is effective in controlling a
disease that can result in suffering and death of the cattle as well as
economic devastation to the producer. The term "subtherapeutic" has been
defined by some to include growth promotion and disease prevention
claims. I would challenge these groups to define exactly where a drug
becomes "subtherapeutic" and therefore incapable of having an effect on
disease. The appropriate use of terms would be to address the drug use
by the label claim of treatment, control, or increase in rate of weight
gain and/or feed efficiency. Where appropriate, a relatively low dose of
an antimicrobial may effectively control disease signs along with the
resulting adverse animal welfare and economic effects. This relatively
low antimicrobial exposure also minimizes the total exposure of normal
and pathogenic bacterial flora to antimicrobials over time.

The "subtherapeutic" categorization attempts to cast all antimicrobial
regimens below an undefined threshold as inappropriate due to selection
of resistant pathogens. In reality, resistant organism selection
pressure is much more complicated than just *"a high concentration for a
short term is good, a lower concentration or a longer exposure is bad"*.
The use of the term "subtherapeutic" indicates a cursory knowledge of
the effects of antimicrobials in food animals as they relate to the
combination of effects on animal well being, disease control, and food
safety. Each application is different, and the attempts to supersede the
regulatory process with blanket legislation prohibiting "subtherapeutic"
uses, however well intentioned, will result in instances where a
decreased ability to address disease pressures in cattle production will
not be offset by a benefit in antimicrobial resistance selection.

I would not propose that the bacterial pathogens in humans and cattle
exist in total isolation from each other, nor would I claim that there
are no possible links between antimicrobial use in cattle and therapy in
humans. However, I would caution that circumventing the approval process
in making leaps from effect back to cause will undermine the ability of
the cattle industry to address disease challenges and in many cases may
result in no benefit to human therapeutics.

Separate scientific risk assessments have been conducted on the uses of
virginiamycin and macrolides in food animals.[^1]^,^[^2] The former
supported by the FDA/CVM and the latter supported by a pharmaceutical
company. Neither risk assessment defined a risk which any reasonable
reviewer would classify as significant. It is absolutely essential to
the wellbeing of animals and humans in the United States that
discussions on antimicrobial resistance be focused on specific drugs,
uses, and pathogens with appropriate data supporting the discussion.
Efforts to cast all food animal antimicrobial uses in the same light are
both misguided and dangerous.

As Congress continues to have an interest in this issue, we recommend
that the focus be put on the tools already in place rather than imposing
new rules, regulations, and prohibitions on animal agriculture. One way
to do this would be to ensure that the National Antimicrobial Resistance
Monitoring System (NARMS) and the Food Animal Residue Avoidance Databank
(FARAD) be fully supported and funded.

NARMS was developed in 1996 to monitor changes in susceptibility of
select bacteria to antimicrobial agents of human and veterinary
importance and is a collaboration between three federal agencies
including FDA's CVM, the Centers for Disease Control and Prevention
(CDC), and USDA.  NARMS also collaborates with antimicrobial resistance
monitoring systems in other countries, including Canada, Denmark,
France, the Netherlands, Norway, Sweden, and Mexico so that information
can be shared on the global dissemination of antimicrobial resistant
foodborne pathogens.  

The NARMS program monitors changes in antimicrobial drug
susceptibilities of selected enteric bacterial organisms in humans,
animals, and retail meats to a panel of antimicrobial drugs important in
human and animal medicine. Bacterial isolates are collected from human
and animal clinical specimens, from healthy farm animals, and raw
product from food animals. Retail meats collected from grocery stores
were recently added to NARMS sampling. A pilot study of animal feed
ingredients collected at rendering plants across the country was also
started in 2002. The CDC and USDA provide the NARMS results annually in
comprehensive summary reports.

The stated goal of NARMS activities is to prolong the lifespan of
approved drugs by promoting prudent and judicious use of antimicrobial
drugs and to identify areas for more detailed investigation.

NCBA feels the program could be improved if the FDA, USDA and CDC worked
more collaboratively; this includes, among other things, division of
funds as well as evaluation of the data. NCBA especially has concerns in
how CDC analyzes and utilizes data. Data analysis should be purely
science-based and without preconceived agendas. There are various
examples of the damage that can be done to industry when Federal
agencies do not cooperatively work together. The cattle industry cannot
afford for Federal agencies to have an unscientific mis-step that can
remove valuable animal health options from our producers.

The issue of antimicrobial resistance is very concerning to cattle
producers. We encourage and advocate for judicious use of all
medications. In fact, NCBA policy supports the *Producer Guidelines for
Judicious Use of Antimicrobials* which have been in place since 1987. In
addition, NCBA participates in the Codex alimentarius task for on
antimicrobial resistance.

Antimicrobial resistance is not a black and white issue. It is a
multi-faceted and extremely complex issue that cannot be solely focused
on the use of drugs in animal agriculture. Unfortunately, animal
agriculture has been a primary target in this fight, with little or no
consideration given by the public to the use, misuse, and mishandling of
human drugs by the general population. To ensure that the issue of
antimicrobial resistance is properly addressed, it is imperative that we
gather accurate, appropriate, and complete data to identify any problems
and all contributing factors. To date, only limited data exists. These
data need to be gathered and scientifically evaluated without bias or a
pre-determined agenda before any further action is taken by Congress. We
need to have strong information on which to base any action that can
impact the use of drugs in animal agriculture.

Related to preventing selection for resistant pathogens is the need to
know the optimal duration of antimicrobial therapy that balances initial
treatment successes, subsequent relapses, and antimicrobial selection
pressure in favor of resistant pathogens. In both human and veterinary
medicine we are lacking critical studies that define optimal duration of
therapy.

FARAD is another valuable tool that Congress and the Administration have
neglected.

Operating since 1982, FARAD is a computer-based system designed to be
utilized by veterinarians and livestock producers in finding information
on drug use and residue problems. During the drug approval process, FDA
establishes drug residue tolerances in order to help keep food safe.
They also establish waiting periods and withdrawal times to determine
how long you must wait for the animal to process and eliminate the drug
from their systems before they can be harvested for food. The
information in this database is invaluable in helping to avoid drug
residue problems and keeping the food supply safe. FARAD also looks at
pesticide and environmental contaminant residue issues. Unfortunately,
the funding for FARAD runs out next week, and unless Congress adds
funding to the continuing resolution, the valuable information it holds
will be gone.

Finally, I would like to talk about the steps the industry has taken to
police ourselves. The Beef Quality Assurance (BQA) program has set forth
recommendations for how cattle producers should use antibiotics to
protect and maintain the health of their animals. BQA was established in
1987 to provide cattle producers with the principles and tools to use
every day to ensure animals are given proper care and attention.

BQA unites producers with experts (animal scientists, veterinarians,
feed suppliers, animal health companies, meatpackers, retailers and
state and federal regulators) to develop management programs using the
latest science and technology to assure proper animal care, beef
quality, and safety. The BQA program provides guidelines for livestock
care and handling, nutrition and veterinary treatment and incorporates
current FDA, Environmental Protection Agency (EPA), and USDA regulations
as well as Hazard Analysis Critical Control Point (HACCP) principles.

Cattlemen can become BQA certified when they meet criteria for quality
beef production set forth in the BQA guidelines. Producers also undergo
continuous training to remain certified. The BQA Manual is the
overarching guideline that provides consistency across the nation, but
states can go beyond national standards to meet state needs and
opportunities. Most states have individual BQA programs that are
tailored to the needs of their particular state beef industry, and can
offer their own certification standards. State certification
requirements vary, but may include third party verification and testing
procedures to ensure good management practices.

Today, BQA influences more than ninety percent of U.S. cattle.
Approximately 185,000 copies of the brochure of NCBA's Care and Handling
Guidelines have been sent to producers, veterinarians, Departments of
Agriculture, and Universities. BQA is not a static program. An advisory
board made up of cattle producers, beef and dairy veterinarians,
University and Extension scientists, meat scientists, auction markets,
and the transportation industry continually work to update and
strengthen the program. NCBA continues to improve this scientifically
based program in order to meet current and future needs of our industry
in order to maintain a healthy cattle population and a safe beef supply
for our consumers.

In conclusion, we find that in today's cattle industry, the need for
animal health interventions that focus on prevention of disease, control
of disease pressure, and therapy of animals with disease is critical to
the success of cattle producers across this country, as well as helping
to keep our food supply safe. However, our industry believes that the
use of these drugs comes with much responsibility, and that is why we
have worked together with our partners in industry to educate and train
cattle producers. The success of programs such as BQA shows our
industry's commitment. This commitment cannot be overlooked by those who
want to end or restrict the use of animal drugs without having any
credible information to base their accusations. That is why we urge
Congress to turn their efforts towards proven tools such as NARMS and
FARAD in helping to keep our animal and human populations healthy, and
to continue to support the established scientific methods for drug
approval and review as the forum in which to evaluate antimicrobial use
in food animals. Thank you for the opportunity to testify today and we
look forward to working with you in the future.

[^1]: Virginiamycin risk assessment. FDA Center for Veterinary Medicine
    website, <http://www.fda.gov/cvm/CVM_Updates/virginiamycinup1.htm>.
    Accessed 9-23-08

[^2]: Hurd HS, Doores S, Hayes D, et al. Public health consequences of
    macrolide use in food animals: a deterministic risk assessment. J
    Food Prot. 2004:67(5):980-992.

    **Michael Douglas Apley**

    111B Mosier Hall

    College of Veterinary Medicine, Department of Clinical Sciences

    Kansas State University, Manhattan, Kansas, 66506

    Work -- 785-532-4167, e-mail -- <mapley@vet.ksu.edu>

    **[Education and Board Certification]{.underline}**

    [Board Certification]{.underline}: Diplomate, American College of
    Veterinary Clinical Pharmacology, July 1994

    [Date Institution Degree]{.underline}\_\_\_

    May 1992 Kansas State University, Manhattan, KS **Ph.D. in
    Physiology (pharmacology)**

    May 1987 Kansas State University, Manhattan, KS **Doctor of
    Veterinary Medicine**

    December 1981 Kansas State University, Manhattan, KS **Bachelor of
    Science**

    **[Positions and Employment]{.underline}**

    **2006-present** Director, PharmCATS Bioanalytical Services, Kansas
    State University

    **2005-present** Associate professor, clinical sciences, Kansas
    State University,

    > Manhattan, KS

    **2004-2005** Interim director, Production Animal Medicine Unit,
    Iowa State University,

    > Ames, IA

    **1996-2005** Assistant/Associate professor, beef production
    medicine, Iowa State University,

    > Ames, IA

    **1992-1996** Veterinary practitioner specializing in feedlots and
    pivotal trial research,

    > Greeley, CO

    **1989-1992** Temporary instructor/graduate student, Kansas State
    University,

    > Manhattan, KS

    **1987-1989** General Veterinary Practitioner, Larned, KS

    **[Other Experience and Professional Memberships]{.underline}**

    **2007-2009** President, American College of Veterinary Clinical
    Pharmacology

    **2004-2005** President, Academy of Veterinary Consultants

    **1999--present** Director, Veterinary Antimicrobial Decision
    Support System

    **1998-2004** Vice chair, Judicious antimicrobial use steering
    committee, American

    > Veterinary Medical Assoc.

    **1996-2001** Board of directors, Academy of Veterinary Consultants

    **1996-2001** Committee on biologic and pharmaceutical issues,
    American Assoc. of

    > Bovine Practitioners

    **1995-2003** United States Pharmacopeia, Expert Advisory Panel on
    Veterinary

    > Medicine

    **[Selected peer-reviewed publications]{.underline}**

    > Lubbers B, **Apley MD**, Coetzee JF, Mosier DA, Biller DS, Mason
    > DE. Use of computerized tomography to evaluate lung pathology in
    > calves. *American Journal of Veterinary Research*. 68:1259-1264,
    > 2007.
    >
    > **Apley MD**, Coetzee JF, Immerman PM, Karriker LA, Gehring R.
    > Ampicillin pharmacokinetics in swine following needle-free,
    > intramuscular, and intravenous administration. *Journal of
    > Veterinary Pharmacology and Therapeutics*. 30(5):417-421, 2007.
    >
    > Rust RL, Thomson DU, Loneragan GH, **Apley MD**, Swanson J.
    > Effects of different castration methods on behavior responses and
    > performance of postpubertal bulls. *Bovine Practitioner*.
    > September, 2007.
    >
    > Coetzee, J.F., Gehring, R., Bettenhausen, A.C., Lubbers, B.L.,
    > Thomson, D.U, KuKanich, B, Toerber, S.E and **Apley M.D**
    > Attenuation of acute plasma cortisol response in calves following
    > intravenous sodium salicylate administration prior to castration..
    > *Journal of Veterinary Pharmacology and Therapeutics*. 30:305-313,
    > 2007.
    >
    > Coetzee, J.F., Schmidt, P.L., **Apley, M.D.,** Reinbold J.B. and
    > Kocan, K.M. Comparison of the complement fixation test and
    > competitive ELISA test for serodiagnosis of *Anaplasma marginale*
    > infection in experimentally infected steers. *American Journal of
    > Veterinary Research*, 68(8):872-878, 2007.
    >
    > Patterson AR, Karriker LA, **Apley MD**, Imerman, PM.
    > Determination of sodium salicylate serum concentrations under
    > typical nursery conditions. *Journal of Swine Health and
    > Production*, 15(3):146-151, **2007**.
    >
    > Coetzee JF, **Apley MD**, Kocan KM. Comparison of the efficacy of
    > enrofloxacin, imidocarb and oxytetracycline for clearance of
    > persistent *Anaplasma marginale* infections. *Veterinary
    > Therapeutics.* 7(4):347-360, **2006**.
    >
    > Coetzee JF, **Apley MD**. Efficacy of enrofloxacin against severe
    > experimental *Anaplasma marginale* infections in splenectomized
    > calves. *Veterinary Therapeutics*. 7(3):319-328, **2006**.
    >
    > Coetzee JF, **Apley MD,** Kocan KM, Jones DE. Flow cytometric
    > evaluation of
    >
    > selected antimicrobial efficacy for clearance of *Anaplasma
    > marginale* in short-
    >
    > term erythrocyte cultures. *Journal of Veterinary Pharmacology
    > and*
    >
    > *Therapeutics*, 29:173-183, **2006.**
    >
    > O'Connor AM, Sorden SD, **Apley MD**. The association between
    > persistently bovine viral diarrhea virus-infected calves and pen
    > morbidity in an Iowa feedlot. *American Journal of Veterinary
    > Research*, 66(12):2130-2134, **2005.**
    >
    > Rosenbusch R F, Kinyon JM, **Apley MD**, Funk ND, Smith S, Hoffman
    > LJ. In vitro antimicrobial inhibition profiles of Mycoplasma bovis
    > isolates recovered from various regions of the United States from
    > 2002-2003. *Journal of Veterinary Diagnostic Investigation*
    > 17:436-441. **2005**
    >
    > Coetzee JF, **Apley MD**, Kocan KM, Rurangirwa FR, Van Donkersgoed
    > J. Comparison of three oxytetracycline regimens for the treatment
    > of persistent *Anaplasma marginale* infections in beef cattle.
    > *Journal of Veterinary Parasitology* 127:61-73. **2005**.
    >
    > Fajt VR, **Apley MD**, Brogden KA, Skogerboe TL, Shostrom VK, Chin
    > YL. Effect of danofloxacin and tilmicosin on body temperatures of
    > beef calves with pneumonia experimentally induced by inoculation
    > with *Mannheimia haemolytica*. *American Journal of Veterinary
    > Research* 65(3): 610-615. **2004**.
    >
    > Wagner SA, **Apley MD**. Effects of two anti-inflammatory drugs on
    > physiologic variables and milk production in cows with
    > endotoxin-induced mastitis. *American* *Journal of Veterinary
    > Research* 65 (1): 64-68. **2004**.
    >
    > Fajt VR, Apley MD, Roth JA, et al. The effects of danofloxacin and
    > tilmicosin on neutrophil function and lung consolidation in beef
    > heifer calves with induced *Pasteurella (Mannheimia) haemolytica*.
    > *Journal of Veterinary Pharmacology and Therapeutics*
    > 26(3):173-180. 2003.
    >
    > Wagner SA, Apley MD. Pharmacodynamics of isoflupredone acetate in
    > an endotoxin-induced mastitis model. *Journal of Dairy Science*
    > 86(3). 2003.
    >
    > Meyer BM, **Apley MD**, Imerman PM. Comparison of serum steroidal
    > hormone concentrations in buller steers, riders, and uninterested
    > pen mates. Investigation of sickness, body weight, feed bunk
    > status, and implant condition during buller occurrence. *Bovine
    > Practitioner* 36(1):27-33. **2002**.

    **[Federal Grants and Contracts since October 1, 2004]{.underline}**

    Coetzee JF, **Apley MD**, Gehring R, White BJ, Anderson DE, Thomson
    DU. Validation of a bovine pain model and development of practical
    and effective pain relief regimens through
    pharmacokinetic-pharmacodynamic modeling. USDA NRI. Awarded May,
    2008. **\$320,000**

    **Apley MD.** The Veterinary Antimicrobial Decision Support System.
    Food and Drug Administration Center for Veterinary Medicine. Period
    of Performance May 1, 2001 to April 29, 2006. **\$1,244,219**