Annual Report of the Minor Use Animal Drug Program
January
1, 2001 to December 31, 2001
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. John Neilson Florida
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
In 2001 a Public Master File for tilmicosin, prepared by
NRSP-7, has been used to extend the label for cattle to include sheep. A complete Public Master File for the use of
oxytetracycline immersion to mark fish otoliths is in the final stages of
review and an announcement of the availability of the data should be published
in the Federal Register soon. Initial
lasalocid efficacy trials in deer and goats were completed. As seen in Table 2, NRSP-7 has supplied data
for 29 published Public Master Files that include 23 drug approvals. These new Animal Drug Approvals and Public
Master File publications involved a combination of 14 animal species and 19
drugs.
Additional work involved the preparation of protocols for
pharmaceutical company review of florfenicol use in sheep. Major progress was made on projects for
control of American Foulbrood in bees.
Both tylosin and lincomycin have been demonstrated to be safe to honey
bees and data will soon be submitted for review. An effectiveness component for carp pituitary
extract was submitted to FDA/CVM for review.
Development of a secure web site for retention of project documents was
completed and an internet database of drugs for minor species was concluded.
A major effort during the past year was to establish
research applicable to multiple species, referred to as species grouping
research, to enhance the efficiency of approving therapeutic compounds for fish
and game birds. In addition, a number of
research studies were completed including:
A.
Human food
safety studies for
a.
(1)
Oxytetracycline in Tilapia,
b.
(2)
Oxytetracycline in Hybrid Striped Bass,
c.
(3) Romet-30
in Summer Flounder, and
d.
(4) Romet-30
in Tilapia;
A.
Target animal
safety studies for
a.
(1)
Oxytetracycline and
b.
(2) Romet-30
in Tilapia and
c.
(3) Rofenaid
in pheasants;
C. Evaluation of Rofenaid for use in small game birds;
D. All in-vivo stages required for the use of fenbendazole
in game birds and fenbendazole residues in game bird tissues;
F. Validation of a modified fenbendazole method received
provisional acceptance;
G. Microsomes from four avian species were collected for
avian species grouping studies; and
H. A protocol for efficacy studies for Pasteuralla multocida in pheasants was developed.
To date 330 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. Currently there are 23 active research projects
involving 12 animal species and 17 different drugs (Table 3). Drug approvals and
active projects by species are depicted graphically in Figure 1. Approximately 35% of the active
projects involve ruminant species, 24% avian, 26% aquatic and 13% other. At 55%, the ruminants represent the largest percentage of
drug approvals in the NRSP-7 program followed by avian at 24%, aquatic at 14%
and other species at 7%.
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; and $550,000 per year for fiscal years 1995-2000; $548,970 in fiscal year
2001.
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; and $87,000 state appropriations and
$38,850 industry contributions in 2001.
In the 20 years of the minor species drug program a total of
$7.9 million has been granted through federal funding and an additional 43%
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
$389,000. This figure is based on the
approvals and Public Master Files listed in Table 2. Average federal expenditures per completed
research for a drug approval or publication of a Public Master File was
$274,000.
Work Planned for Next Year
Current aquaculture projects
include hydrogen peroxide for bacterial gill disease in finfish,
oxytetracycline for finfish, sulfadimethoxine/ormetoprim (Romet-30™) for
finfish. Sulfadimethoxine/ormetoprim
(Rofenaid™) for pheasants is also underway.
A project will be started in the coming year for florfenicol in sheep
and goats for bacterial respiratory infections and possibly for a foot rot
claim. A new project with imidocarb for
babesiosis in cattle is projected, but not certain pending sponsor
agreement. Additionally, Apitol for bees
to treat varroa mites, florfenicol for mycoplasma infections in veal calves,
and a treatment for mastitis in ewes have been proposed as new projects for the
coming year.
Publications Issued or
Manuscripts Approved During the Year
Submitted:
John G. Babish, Ph.D. Date
National Coordinator
Chair, Technical Committee
Donald C. Robertson, Ph.D. Date
Chair, Administrative Advisors