Annual Report of the Minor Use Animal Drug
Program
January
1, 2000 to December 31, 2000
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. John. T. Neilson Florida AES
Dr. David Thawley Nevada 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. Robert Holland 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 2000, three Public Master Files (PMF) on minor use drugs
were published in the Federal Register,
indicating approval by CVM of NRSP-7 data; they were (1) albendazole for liver
flukes in goats, (2) ceftiofur for bacterial pneumonia in goats, and (3)
tilmicosin for chronic respiratory disease in sheep. As seen in Table 2, NRSP-7 has supplied data for
29 published Public Master Files including 23 drug approvals. These New Animal Drug Approvals and Public
Master File publications involved a combination of 14 animal species and 19
drugs. The PMF publication enables
pharmaceutical companies to extend their label claims to minor species by
referencing the published PMF in their NADA filing. Furthermore, these data also enter the public
domain as presentations to professional groups, publication of peer-reviewed
articles and inclusion in the Food Animal Residue Avoidance Databank (FARAD).
To date 323 drug
requests have been submitted to NRSP-7 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). Approximately 35% of the active projects
involve ruminant species, 26% avian, 26% aquatic and 13% other species. Drug approvals and active projects by species
are depicted graphically in Figure 1. 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%.
The demands on the program
continue to increase for several reasons.
New requests are received for additional species, including non-food
species and expanding industries such as ostrich and emu. There is increased pressure on the Minor Use
Animal Drug program to include the development of production drugs such as
spawning hormones for certain aquaculture industries. Increased costs also are being incurred due
to the need for research laboratories to comply with federal requirements for
Good Laboratory Practices (GLP). More
expensive analytical techniques and sophisticated research are required
especially to assure human and target animal safety.
In addition to the
development of data for FDA review, the NRSP-7 program initiated a species
grouping program. Designed to make the
drug approval process more efficient for all minor species, research was begun
that will enable game birds and fish to be evaluated on the basis of one
or two marker species. With species grouping, safety and efficacy
studies of a drug in one species could be extrapolated to other species within
the same group. Considering that the
aquatic and game bird classes contain at present 10 and 8 economically
significant production species, respectively, rates of PMF publications could
be increased several-fold on the expenditure of funds for just one marker
species. For example, grouping of 4 to 8
species from either the aquatic or game
bird classes would increase the annual
PMF filings by 4- to 8-fold.
The regional coordinators and investigators will complete
the research for three to four additional animal drug studies in each of the
next two years. It is anticipated that
the research in progress will result in three new minor use animal drug
approvals in 2001 and again in 2001.
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.
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; and $349,250 state appropriations and $9,500
industry contributions in 2000.
In the 19 years of the minor species drug program, a total
of $7.391 million has been granted through federal funding and an additional 45
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
$337.000 based on the listing in Table 2.
Average federal expenditures per completed research for a drug approval
or publication of a Public Master File was $256,000.
Work Planned for Next Year
The regional coordinators and investigators will complete
the research for three to four additional animal drug studies in each of the
next two years. It is anticipated that
the research in progress will result in three new minor use animal drug
approvals in 2001.
Publications
Issued or Manuscripts Approved During the Year
Tort, M.J.
(2000) Studies of Hydrogen Peroxide for the Treatment of Bacterial Gill
Disease in Fish. PhD Dissertation,
Cornell University, Ithaca, New York 185 pp.
Submitted:
John G. Babish, Ph.D. Date
National Coordinator
Chair, Technical Committee
Donald C. Robertson, Ph.D. Date
Chair, Administrative Advisors