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October 31, 2008

Division of Dockets Management (HFA-305)

Food and Drug Administration

5630 Fishers Lane, rm. 1061

Rockville, MD 20852

Re: Docket No. FDA-2008-N-0326 New Animal Drugs; Cephalosporin Drugs;
Extralabel Animal Drug Use; Order of Prohibition

The American Association of Swine Veterinarians (AASV) welcomes the
opportunity to comment on the Order prohibiting the extralabel use of
cephalosporin antimicrobial drugs in food-producing animals (Docket No.
FDA-2008-N-0326) issued July 3, 2008 by the Food and Drug
Administration's Center for Veterinary Medicine (CVM).

The AASV wishes to express the concern of our veterinary members
regarding FDA's order prohibiting the extralabel use of the entire class
of cephalosporin antimicrobials in food-producing animals. This decision
has significant implications for swine veterinarians faced with the
challenge of devising treatment regimens to alleviate animal suffering,
enhance food safety and protect public health.

There are relatively few approved antimicrobials to treat the myriad of
conditions encountered by swine veterinarians daily. A number of
conditions exist for which there are no approved or effective
antimicrobials thus prompting the need for extralabel use as allowed
within the context of the Animal Medicinal Drug Use Clarification Act
(AMDUCA).

AMDUCA was enacted to address the recognized need for food animal
veterinarians to access a wider spectrum of antimicrobial products to
facilitate the treatment of animals under their care. The act recognizes
veterinarians' extensive education, training and licensure as
qualifications affording them the responsibility inherent in the
decisions necessary to prescribe antimicrobials in a judicious manner
and to understand the animal health and human health implications of
their actions. Under the provisions of AMDUCA, the extralabel use of
these products is strictly controlled and requires the application of
significant safeguards designed to protect public health and promote the
continued effectiveness of critically important antimicrobials. While
delineating the mechanism by which veterinarians can prescribe
antimicrobials in an extralabel manner, the act also allows for FDA to
exert additional controls and restrictions over such use if the agency
determines that safe levels for residues or tests to detect residues can
not be determined. Based on the statutory language of S.340, AMDUCA is
not be the appropriate vehicle for the reduction of cephalosporin usage
in food animals for issues related to drug resistance.

In the case of the cephalosporin class of drugs, the FDA has chosen to
enact a broad overarching total ban on the extralabel administration of
this entire class of products in all food animal species, even in those
species for which there are approved uses. This leaves swine
veterinarians with one less critical category of antimicrobial products
from which to choose when deciding how to effectively treat the animals
for which they are responsible. This expansive ban may actually endanger
the public health FDA is trying to preserve.

In making this decision, FDA determined that the extralabel use of
cephalosporins will "likely cause an adverse event and as such presents
a risk to the public health." The agency based this determination on
domestic and international surveillance systems (such as NARMS) as well
as FDA investigational findings. We disagree that the data cited support
a determination that the extralabel use of the cephalosporin class of
antimicrobials in swine presents a risk to public health. Surveillance
programs, such as NARMS, have shown that there is an extremely low
incidence of Salmonella and E. coli in pork samples collected at
slaughter which is a testament to the efforts of swine veterinarians and
pork producers. It has been shown that cephalosporin-resistant E. coli
and Salmonella are multi-drug resistant and cross-resistant to many
β-lactam class drugs. Thus, the presence of cephalosporin-resistant
bacteria does not necessarily indicate that cephalosporin use is
contributing to this resistance. A number of studies have found
cephalosporin resistant bacteria in animals that have never received
antimicrobials let alone cephalosporins. This raises significant
questions on how effective the ban will be even if use of cephalosporins
is decreased.

In addition, data presented to FDA during the ceftiofur approval process
indicates that the drug is minimally active in the environment following
excretion by the animal with a very low selection pressure for resistant
organisms. Since 1998, Pfizer Animal Health has been conducting an
ongoing multi-center program to evaluate susceptibility trends of
pathogens against ceftiofur. The results of nine years of monitoring
found that none of the swine respiratory disease isolates collected have
tested resistant to ceftiofur.

Swine veterinarians and pork producers take the use of all
antimicrobials seriously. AASV members have adopted the AVMA's Judicious
Therapeutic Antimicrobial Use Guidelines and have collaborated with the
National Pork Board and the FDA on the development of programs such as
Pork Quality Assurance and Take Care -- Use Antibiotics Responsibly™ to
educate producers about the appropriate use of antimicrobials. Due to
the cost of these drugs and the concerns associated with their use,
antimicrobials are not the only tool, or even the first tool, used in
the treatment of disease. An effective herd health management strategy
considers all aspects of herd management including environment, diet,
ventilation, biosecurity, and vaccination in an effort to prevent the
introduction and transmission of pathogenic organisms.

Veterinarians follow a well-defined algorithm when deciding to use
antimicrobials in an extralabel manner. An accurate clinical diagnosis
is made with subsequent laboratory confirmation of the pathogens present
and testing of bacterial susceptibility to antimicrobials . Based on the
results of the antibiogram and the experience of the practitioner, a
disease management/control plan is formulated which may include the use
of antimicrobials to treat, control and prevent disease. Approved
products are the first choice if the use of antimicrobials is deemed
necessary. If there are no approved or effective labeled products,
veterinarians are forced to consider prescribing the use of an
antimicrobial in an extralabel manner. They do so under the guidelines
of AMDUCA and within the context of a veterinarian-client-patient
relationship. Veterinarians prescribing the extralabel use of an
antimicrobial also apply additional safeguards, such as an extended
withdrawal period, to minimize the risk to public health.

When faced with the necessity to use drugs in an extralabel manner, it
is our opinion that the safest choice is to use a drug approved for the
target species to treat a non-labeled condition. The pharmacokinetic
properties of an approved compound in swine are well-known and include
proper dose, tissue distribution, metabolite formation, excretion,
routes of administration and appropriate withdrawal times to avoid
violative residues. It seems preferable to utilize these products rather
than selecting a drug not approved for use in swine where information
may be incomplete or lacking.

We believe it is possible to modify the Order to address FDA's concerns
regarding resistance without unduly encumbering veterinarians in their
efforts to provide effective treatments for their patients. We offer the
following suggestions for FDA consideration and action:

-   Continue to allow the extralabel use of veterinary cephalosporins in
    accordance with AMDUCA to treat indications not listed on the label
    in the species for which the drug is approved at the approved dosage
    via the approved route of administration.

-   Continue to work with CDC, USDA, pharmaceutical manufacturers and
    stakeholder groups to explore the implications of antimicrobial use
    in humans, companion animals and food animals with regard to the
    development of resistant organisms. Research should be targeted to
    identify those specific practices which can be shown to contribute
    to resistance development and regulations should be enacted to
    restrict, ban or control those specific practices.

-   Establish regulations in an open and transparent manner based on the
    results of scientifically-sound data and risk-based assessments.

-   Establish and promote a stream-lined efficient process by which
    pharmaceutical manufacturers might add supplemental indications to
    existing label claims to reduce the need for extralabel use.

The imposition of a complete ban on the use of cephalosporin class drugs
undermines AMDUCA and ignores the veterinarian's ability to use these
products in a responsible and judicious manner. Without modification,
this Order unduly restricts the veterinarian's ability to determine the
most appropriate and effective treatment for their patients,
particularly when no FDA approved or effective antimicrobial alternative
exists. The unintended consequences of this Order may well be increased
animal suffering, decreased food safety and adverse impacts on public
health.

In conclusion, the AASV appreciates the opportunity to comment on this
Order. It is our opinion that the broad ban enacted by FDA will not
accomplish the goal of reducing multi-drug resistance in foodborne
pathogens. We encourage FDA to seriously consider the impact of this ban
on animal health and welfare as well as the potential unintended
consequences to food safety, public health and animal suffering. We
believe that extralabel restrictions based on the suggestions outlined
above are justified and request the agency consider modifying the Order.