Annual Report of the Minor Use Animal Drug Program
January 1, 2002 to December 31, 2002
Project: NRSP-7 A National Agricultural Program to
Approve Animal Drugs for Minor Species and Uses
Cooperating Agencies
and Principal Leaders:
US Department of Agriculture/CRESS
Dr. Larry R. Miller USDA/CRESS Representative
US Food and Drug Administration/Center for
Veterinary Medicine
Dr. Meg R. Oeller FDA/CVM Liaison
Administrative Advisors
Dr. Donald. C. Robertson (Chair) Kansas AES
Dr. Kirklyn M. Kerr Connecticut AES
Dr. David Thawley Nevada AES
Dr. Gary Adams Texas
AES
National Coordinator
Dr. John G. Babish New York AES
Regional Coordinators
Dr. Arthur L. Craigmill California AES
Dr. Paul R. Bowser New York AES
Dr. Alistair I. Webb Florida AES
Dr. Ronald W. Griffith Iowa AES
Background and Organization of NRSP-7
In 1982, a national program for approval of minor
use animal drugs was established by the United States Department of Agriculture
(USDA). The program was originally part
of the Interregional Project Number 4 (IR-4) for clearance of compounds to
control diseases and pests of both plants and animals. In 1993 a separate project, National Research
Support Project No. 7, for minor use animal drug approval was established by
CSRS (now CSREES).
NRSP-7 is composed of a Technical Committee and four Administrative Advisors representing State Experiment Station Directors. These Administrative Advisors provide liaison between the Directors of the State Experiment Stations, USDA/CSREES, FDA/CVM, various animal organizations, and others coordinating the efforts of this program. The Administrative Advisors provide input on policy, budget and administrative matters.
Usefulness of NRSP-7
Agricultural production of fish, game birds, sheep, goats, ratites and
deer in the United States is critically important to numerous regional
economies in the United States. This
diverse aggregation of “Minor Species” represents $2 billion in local US farm
revenues annually. Individually, however,
these minor species represent drug markets too small to provide a sufficient
return on the high cost of developing a new drug application. Therefore, few approved drugs are available
to treat diseases in these species. The
shortage of dugs for minor animal species and minor uses is a problem well
recognized by animal producers, veterinarians, animal scientists and
regulators. In a sense, minor animal
drug uses are analogous to human orphan drug uses, for which the market is
insufficient to justify costly research expenditures necessary to obtain FDA
approval. Minor uses include drugs for
sheep, goats, fish, game birds, rabbits, ratites and deer. Minor uses also include diseases in major
species such as cattle, swine, chickens and turkeys that occur infrequently or
in limited geographical locations.
NRSP-7 is designed to address this shortage of minor use animal drugs
by funding and overseeing the efficacy, animal safety, human food safety
research and environmental risk assessment required for drug approval.
The scope of the program includes animals of agricultural importance
and generally excludes companion animals. While this continues to remain the
dominant goal of the program, research has expanded or given additional
emphasis to aquaculture species, veal calves and sheep. Additional demands on the NRSP-7 program include
new animal industries such as ostrich and emus, non-food species within
agriculture practices, disease transfer from non-agricultural species to
domestic species, and food and environmental safety.
The program provides coordination of efforts by animal producers, drug
manufacturers, FDA/CVM, USDA/CSREES, other government agencies, universities,
state Agricultural Experiment Stations, and veterinary schools to get the job
done. NRSP-7 is a prime example of
Federal interagency collaboration in coordination with academic institutions,
pharmaceutical industries and commodity interests to effectively meet an urgent
public health need.
Now, with the
increased public sensitivities about food safety and environmental protection,
there is an even greater need for continuation of these ongoing projects. This program is the only currently active
initiative that generates information on the safe and effective use of
antimicrobials in such a wide range of species.
Through NRSP-7, producers and veterinarians can have the necessary
information to reduce pain and suffering in these commercially important minor
species.
How NRSP-7 Operates
In order to fulfill its mission, NRSP-7 functions through
the coordination of efforts among animal producers, pharmaceutical
manufacturers, FDA/CVM, USDA/Cooperative State Research, Education, and
Extension Service, universities, State Agricultural Experiment Stations and
veterinary medical colleges though out the country. The steps involved in this coordination of
efforts are described in Table 1.
·
Funding
Research for the Minor Use Animal Drug Program is funded through a USDA special research grant administered by NRSP-7. Support for NRSP-7 also comes from pharmaceutical companies, universities, and State Agricultural Experiment Stations.
·
Research
Research projects are
initiated by requests, usually from researchers or animal producers, to the
program’s regional coordinators to address a particular minor use drug
need. These requests, known as ADRs
(Animal Drug Requests), are prioritized according (i) to financial and
regulatory feasibility, (ii) to importance to the animal industry, and the
pharmaceutical manufacturer’s commitment to the minor use drug approval. Once a request is accepted as a research
project, study protocols are developed and reviewed by FDA/CVM. All research projects are conducted in
accordance with FDA’s Good Laboratory Practices regulations.
·
FDA Approval
A successful research project is submitted to FDA’s Center
for Veterinary Medicine for review and inclusion in a Public Master File. The availability of the data for use on a
label claim is announced through publication of the Public Master File in the Federal Register. A pharmaceutical sponsor may then reference,
at no cost, the data in the Public Master File to support a new animal drug
application for the minor use. The final
step in the process is FDA approval of this application for the pharmaceutical
sponsor, so that the product may be labeled and sold for minor use.
Progress of the Work and Principal
Accomplishments
NRSP-7 has been responsible for 30 Public Master
File (PMF) publications in the Federal
Register, an average of 1.4 per year during its twenty-one years of funding
(Table 2). These Public Master Files
have supported FDA approval for 23 products.
In 2002, the PMF for otolith marking of fish was completed and
filed. At this time, two pharmaceutical
companies have stated their intention to file NADAs for the product. Unfortunately, there are completed projects that the pharmaceutical
companies have not picked up for label claims.
These Public Master Files include Merial’s clorsulon for goats, and
Pfizer’s albendazole for goats and amoxicillin for sheep. An NADA for tilmicosin in sheep was completed
and submitted to FDA/CVM for review.
Additionally, NRSP-7 has completed the target animal safety and
antimicrobial resistance components for honeybee studies with lincomycin and
tylosin for Varroa mite infection.
Effectiveness studies for Carp Pituitary extract as a spawning aid for
various fish have been concluded.
Currently there are 34 active research projects
involving 15 animal species and 23 different drugs (Table 3). Approximately 35% of the active projects
involve ruminant species, 40% avian, 15% aquatic and 10% other. A comparison of the relative distribution of
research on active projects by species to previously published Master Files is
presented in Figure 1. While a majority
of Public Master Files (53%) involved ruminant species, current active projects
are more evenly divided between ruminants and avian species, respectively, 35
and 40%. Drug approvals and current
research on aquatic species remains relatively consistent with 17 and 15% for
aquatic species, respectively.
Similarly, other species represent 7% of drug approvals and 10% of
current active projects.
To date 331 drug requests have been submitted to
the Minor Use Animal Drug Program for the development of data in support of the
submission of a New Animal Drug Approval (NADA). Through
a prioritization process that has included (i) constraints imposed by concerns
of antimicrobial resistance, (ii) limitations of availability of certain
expensive or rare animal species, (iii) appropriate efficacy models, and (iv)
high risk/benefit liabilities and lack of economic incentive for certain
pharmaceutical manufacturers, the number of highest priority projects has been
estimated at 32. Added to our 34 current
active projects, the backlog of projects represents a research commitment
stretching over several decades.
Funding
The breakdown of funding by source for NRSP-7 is presented in Table
4. Since 1982, grants have been awarded
from appropriated USDA funds in the amount of $240,000 per year for fiscal
years 1982-85; $229,000 per year for fiscal years 1986-1989; $226,000 for
fiscal year 1990; $450,000 for fiscal year 1991; $464,000 per year for
fiscal years 1992 and 1993; $611,000 for fiscal year 1994; $550,000 per year
for fiscal years 1995-2000; $548,970 in fiscal year 2001; and $588,000 in
fiscal year 2002.
The non-federal funds and sources provided for NRSP-7 since
1991 included $156,099 state appropriations, $29,409 industry contributions and
$11,365 miscellaneous in 1991; $265,523 state appropriations, $1,182 product
sales, $10,805 industry contributions and $59 miscellaneous in 1992; $212,004
state appropriations, $315 industry contributions and $103 miscellaneous in
1993; $157,690 state appropriations and $7,103 miscellaneous in 1994; $84,359
state appropriations in 1995; $191,835 non-federal support in 1996; $357,099
non-federal support in 1997; $104,596 state appropriations and $97,375 industry
contributions in 1998; $317,225 state appropriations and $9,678 industry
contributions, and $7,000 miscellaneous in 1999; $349,250 state appropriations and
$9,500 industry contributions in 2000; $87,000 state appropriations and $38,850
industry contributions in 2001; and $137,720 state appropriations and $30,480
industry contributions in 2002.
In the 21 years of the minor species drug program, a total of $8,527,790 has been granted through federal
funding and an additional 42 percent, on average, has been obtained through
nonfederal funds. The average
total expenditure per completed research for a drug approval or publication of
a Public Master File was $367,000. This
figure includes three submissions currently under review at FDA/CVM as well as
the 30 projects listed in Table 2.
Average federal expenditures per completed research for a drug approval
or publication of a Public Master File was $258,000.
Work Planned for Next Year
The residue depletion analyses and target animal safety
report for fenbendazole for pheasants and partridges have been completed; it is
estimated that a submission of the package of studies for these two species to
FDA/CVM will be in early 2003. The PMF
publication and pharmaceutical company filing of the NADA would probably be by
late spring. Additionally, target animal
and human food safety studies of oxytetracyline and sulfadimethoxine/ormetoprim
in hybrid striped bass, summer flounder, tilapia and channel catfish have been
completed and the data are to be submitted to FDA/CVM by late spring.
New projects initiated with pharmaceutical company
assistance include as Nuflor in sheep and goats. A quality control method for carp pituitary
gland extract will also be completed and allow for the approval of carp
pituitary gland extract as a spawning aid for channel catfish.
Research on the active projects listed in Table 3 will
continue into the next several years with the goal of publishing Public Master
Files and ultimately having the use placed on a manufacturer’s label so that
the animal industry can use an approved drug insuring safety of the food
product.
Publications Issued or
Manuscripts Approved During the Year
Payne, M.A., Babish, J.G.,
Bulgin, M., Lane, M., Wetzlich, S. and Craigmill, A.L. (2002) Serum pharmacokinetics and tissue and milk
residues of oxytetracycline in goats following a single intramuscular injection
of a long-acting preparation and milk residues following a single subcutaneous
injection. Journal of Veterinary Pharmacology and Therapeutics, 25(1)25-32.
Submitted:
John G. Babish, Ph.D. Date
National Coordinator
Chair, Technical Committee
Donald C. Robertson, Ph.D. Date
Chair, Administrative Advisors