Animal & Veterinary
NRSP-7 Holds Semi Annual Committee Meeting
by Meg Oeller, D.V.M.
FDA Veterinarian Newsletter January/February 2002 Volume XVII, No 1
The USDA's Minor Use Animal Drug Program, National Research Support Project #7 (NRSP-7) held its semi-annual meeting of the technical committee and administrative advisors on October 22 and 23 in Rockville, MD and Washington, DC. The spring meeting is hosted each year by one of the four regions, but the fall meeting is always held in the Washington area to provide an opportunity for input from members of FDA's Center for Veterinary Medicine (CVM).
The purpose of the NRSP-7 Minor Use Animal Drug Program is to address the shortage of minor use animal drugs by funding and overseeing the efficacy, animal safety, and human food safety research and environmental assessment required for drug approval. The scope of the program includes minor species of agricultural importance, and generally excludes companion animals.
The technical committee is made up of a National Coordinator, 4 Regional Coordinators, 4 Regional Administrative Advisors, and liaisons from USDA and FDA. The National Coordinator is Dr. John Babish (Cornell University). The Regional Coordinators are Dr. Arthur Craigmill (University of California, Davis), Dr. Alistair Webb (University of Florida), Dr. Robert Holland (Iowa State University), and Dr. Paul Bowser (Cornell University). The Administrative Advisors are Dr. Kirklyn Kerr (University of Connecticut), Dr. John Nielson (University of Florida), Dr. David Thawley (University of Nevada), and Dr. Don Robertson (Kansas State University). The USDA representative is Dr. Larry Miller (Washington, DC) and the FDA liaison is Dr. Meg Oeller (Rockville, MD). This meeting was also attended by the National NADA coordinator for Aquaculture, Rosalie "Roz" Schnick and Dr. Mark Feldlaufer of the USDA Bee lab in Beltsville, MD, as well as by reviewers and managers from FDA/CVM.
This meeting was postponed from its originally scheduled dates in September due to the upheaval in travel arrangements following September 11. Because of the change, three of the four administrative advisors were unable to attend. Dr. Don Robertson was their sole representative at this meeting.
Welcoming Remarks From Dr. Sundlof
The Director of CVM, Dr. Stephen Sundlof, welcomed everyone and explained that the coming year looks very promising for the Center with a proposed budget increase. He pointed out that CVM was still working under a continuing resolution pending passage of the budget. In the next year, a high priority will be on-farm and feed mill inspections based on Bovine Spongiform Encephalopathy (Mad Cow) concerns.
Strategic planning at CVM is starting again with an emphasis on "back to basics". Some items of special interest include controlling internet pharmacies, reduction of the application backlog through the use of consultants to find efficiencies, and the development of tolerances & testing for residues in imported foodstuffs. A contract has been awarded to ICF Consulting to identify medications used in aquaculture around the world. The U.S. is concerned about a competitive disadvantage compared to overseas producers, especially in the case of seafood from Southeast Asia. Some of this may be corrected by the requirement for exporters to have Hazard Analysis Critical Control Point (HACCP) plans in place, since such plans require disclosure of medications used on farmed fish.
Antimicrobial resistance development remains a major concern. A new guidance document is planned for publication in the Spring. Dr. Sundlof noted that there are still problems enforcing prudent use of antibiotics. Links are being established with State veterinary boards to assist with enforcement in the areas of prudent use of antibiotics, compounding, and catalog sales. Dr. Sundlof also said that CVM has received a special allotment of $3 million for studies on subtherapeutic drug use. He was questioned about the advisability of NRSP-7 pursuing a project for florfenicol in sheep. He answered that antimicrobial resistance requirements should not be sufficient to discourage such a project.
National Coordinator's Report
Dr. Babish reported on his meeting with the North Eastern Experimental Station Directors. He was encouraged to make visits to other regions to make sure they are aware of the program. The Southern region will need special attention as they face the future retirement of Administrative Advisor John Neilson and select his replacement.
The new NRSP-7 brochures have been printed but the web site address was inadvertently omitted. A label with the address will be affixed to the brochure before they are distributed. The brochure includes a description of the program's mission, background, and organization as well as a list of the contact information for the members of the technical committee and administrative advisors. On the back of the brochure is an abbreviated Animal Drug Request form so that interested persons may suggest new projects for the program to pursue.
Administrative Advisors' Report
Dr. Don Robertson said that John Babish sent NRSP-7 update letters to major stakeholders in the sheep, goat, gamebird, and aquaculture industries. He advised that we should make an effort to maintain and expand such relationships.
USDA Representative's Report
Dr. Miller related that the USDA budget is on hold. The House budget is the same as last year but the Senate shows an increase. He described the plan for the next day's meeting with administrators at USDA and the order of presentations that we should give.
Regional Coordinators' Reports
NORTHEAST REGION: Dr. Paul Bowser.
Although many of these projects are intended to support species grouping, the data will be accumulated to support individual drug approvals for the drugs under study. Current projects include hydrogen peroxide for bacterial gill disease in finfish, oxytetracycline for finfish, sulfadimethoxine/ormetoprim (Romet-30TM) for finfish and sulfadimethoxine/ormetoprim (RofenaidTM) for pheasants.
SOUTHERN REGION: Dr. Alistair Webb
Dr. Webb reported that current projects include ivermectin for rabbits, fenbendazole for deer, lasalocid for deer and goats, fenbendazole, nitarsone, and zoalene for gamebirds, and carp pituitary extract for fish.
Most discussion centered on Dr. Kelly's (Mississippi State University) proposal to complete the carp pituitary extract target animal safety work. Dr. Kelly proposed both extension of species covered as well as an extensive list of tissues for histopathology. NRSP-7 has provided administrative assistance, but has not funded this work previously. The consensus at the meeting was that it is a needed production tool and should be supported.
NORTH CENTRAL REGION: Dr. Robert Holland
The major current project is the CIDR-G intravaginal progesterone device for sheep. There have been numerous complications of the project resulting from the sale of the device from the original New Zealand manufacturer. We hope to resolve these problems so that this approval can be pursued. The U.S. sheep industry lists this product as its number one need.
WESTERN REGION: Dr. Arthur Craigmill
Dr. Craigmill reported on several completed and inactivated projects. Those completed include a pharmacokinetic study for ceftiofur in alpacas and llamas and another on pharmacokinetics and residue depletion of oxytetracycline in sheep.
Current projects include ivermectin pour-on for bison, strontium chloride in salmonids, and pirlimycin for dairy goats. The bee projects were discussed later by Dr. Feldlaufer. Some species grouping work is underway in gamebirds.
Active NRSP-7 Projects
|Drug||Route of Administration||Species||Indication||Region|
|TYLOSIN||soluble powder||honey bees||American foulbrood||W|
|TILMICOSIN||injection||veal calves||respiratory infections||NC|
|HYDROGEN PEROXIDE||topical||various fish||bacterial gill disease||NE|
|CARP PITUITARY||injection||various fish||spawning aid||S|
|oral (feed)||pheasants||bacterial infections and coccidiosis||NE|
|FENBENDAZOLE||oral (feed)||pheasants, partridges & quail||gapeworm, capillaria||S|
|OXYTETRACYCLINE||oral (feed)||finfish||bacterial infections||NE|
|STRONTIUM CHLORIDE||immersion||finfish||otolith marking||W|
|LINCOMYCIN||soluble powder||honey bees||American foulbrood||W|
|oral (feed)||finfish||Bacterial infections||NE|
Northeast Region _ A new project is planned for goats, although the details are not yet determined.
Southern Region _ A new project with imidocarb for babesiosis in cattle is projected, but not certain pending sponsor agreement.
North Central Region _ Three new projects have been proposed. Final decisions are pending additional information. The proposed projects are for Apitol for bees to treat varroa mites, florfenicol for mycoplasma infections in veal calves, and a treatment for mastitis in ewes.
Western Region _ A new project will be started in the coming year for florfenicol in sheep & goats for bacterial respiratory infections and possibly also for a foot rot claim.
Dr. Mark Feldlaufer of the USDA bee lab in Beltsville discussed his work in support of New Animal Drug Applications for lincomycin and tylosin for American foulbrood in honeybees. The target animal safety study data have been submitted, the residue depletion studies are done, and effectiveness studies are underway. Dr. Oeller has obtained letters from CVM agreeing that antimicrobial resistance studies will not be needed for these projects. The environmental assessments are in progress.
Roz Schnick distributed her handout, "Update on the Activities of the National Coordinator for Aquaculture New Animal Drug Applications." She described the progress of the active projects of the Federal-State Aquaculture Drug Approval Partnership Project. These projects include claims for Aqui-STM (anesthetic), Chloramine-T, Copper Sulfate, Florfenicol, hydrogen peroxide, and oxytetracycline. This group is also conducting studies to support species grouping.
FDA'S NRSP-7 Liaison Report
The Minor Use/Minor Species Animal Health Act of 2001 (the MUMS Bill) has been introduced in both houses of Congress and is continuing to add co-sponsors. If enacted, this legislation would make incentives available to pharmaceutical sponsors, allow for conditional approvals of MUMS drugs, and allow legal marketing of some products for non-food-producing animals under an indexing system.
Current projects were reviewed and some were reclassified as `inactive' for the time being. The committee discussed Investigational New Animal Drug (INAD) investigators who are not producing or submitting their data. In some cases, producers/collaborators might more appropriately get the drugs under the new Compliance Policy Guide on extralabel use of drugs in feed for minor species (CPG 615.115). Those groups should either continue to submit effectiveness data whenever they use the drug under the INAD, or they should use the CPG to acquire needed medicated feeds. Other groups that are studying drugs under an NRSP-7 INAD and not submitting data at all must either submit the data as promised, or have the INAD file inactivated.
It is important that NRSP-7 follow the rules that allow unapproved uses of these drugs under its INADs. It is imperative that this data, including Notice of Claimed Investigational Exemption forms, be submitted in a timely manner so that inspections can be scheduled, and slaughter authorizations can be kept up to date. CVM can take regulatory action against sponsors and investigators who fail to comply with these requirements. NRSP-7 must administer its INAD files in full compliance with the laws and regulations.
This concept involves demonstrating, usually through pharmacokinetics, that similar species may be grouped for the purposes of demonstrating effectiveness, target animal safety, and human food safety. One outcome may be that a representative species can be studied to provide data to support the inclusion of similar species on the label of a new animal drug. This is probably most needed in aquaculture where there are literally hundreds of species and it is not practical to test the drug on them all. Other groups also could benefit from such research. This includes gamebirds (pheasants, partridges, and quail), deer (white tail, red deer, elk, etc.), and ratites (ostriches, emus, and rheas). It may be that the research will show that the species are not similar, or are not similar for some classes of drugs. Learning what is and is not suitable for grouping will be very valuable in making drug approval for minor species more efficient.
Dr. Renate Reimschuessel explained the CVM's Office of Research strategy in the pursuit of rational species grouping. They are studying multiple species (trout, tilapia, catfish, yellow perch, toadfish, salmon); under varying conditions (warm & cold/fresh & sea water); using multiple drugs (albendazole, ivermectin, flumequine). They are looking at drug levels in muscle. Badaruddin Shaikh presented data for albendazole in trout and tilapia (the sulfoxide and sulfone are the metabolites measured).
Dr. John Babish also discussed his species grouping approach. He is looking at characterizing species by drug metabolism ability with emphasis on P450 & CYP families. He is characterizing these with western blot & enzymatic analysis. The fish species he and Dr. Bowser are studying are rainbow trout, tilapia, walleye, yellow perch, summer flounder, hybrid striped bass, and channel catfish. The human based enzyme antibody assays cross-react with fish and gamebirds (quail).
This discussion centered on inspections and the mechanism of a data audit. Dr. Lynn Friedlander, of CVM, explained the requirements for inspections, mechanisms for data audits, and information that should be included in human food safety data submissions. It was a very useful discussion.
Spring 2002 Meeting
The Spring meeting of the NRSP-7 Technical Committee and Administrative Advisors will be held in Davis, California on April 29 and 30, 2002. There will be a tour of the University's sheep dairy followed by the business meeting.
The second day of the meeting was held at the USDA Waterfront Offices. This meeting was attended by the NRSP-7 members and Roz Schnick. Midmorning, the group was joined by USDA administrators.
The NRSP-7 program traditionally hosted a workshop on a minor species concern every 2 years. The last workshop was held in 1996 on the topic of "Drug Approval for Minor Species in the 21st Century". After 1996, resources were directed toward activities other than the sponsorship of workshops. The program planned to hold a workshop next September or October at a hotel in the Dulles airport area.
The committee decided to postpone the workshop until September 2003 in view of overseas travel fears. Dr. Webb and Dr. Craigmill are co-chairing the meeting. They circulated a draft program outline. The current plan is to have the workshop center on international issues for minor species and minor uses. The meeting will be held in cooperation with Global FARAD (the Food Animal Residue Avoidance Databank). The committee will investigate holding the workshop in Baltimore.
Meeting with USDA Administrators
The group then met with Gary Cunningham, Ted Wilson, Bill Wagner, Gary Jensen, and Dave Morris of USDA. Several members of the committee gave presentations on the NRSP-7 program, including, background on the program, species grouping efforts, species project summaries, and the role of FDA/CVM. A productive discussion followed.
Dr. Webb provided an overview of the new and improved NRSP-7 website: http://www.nrsp-7.org. The website currently provides links to minor species group websites, updated names and addresses of committee members, interactive Animal Drug Request Forms for new project requests, and a "Frequently Asked Questions" section. Plans are underway to implement features including "Breaking News", feature articles, a searchable database of animal drugs, and a searchable database of NRSP-7 activities. Please visit the site.
The day-and-a-half meeting was an excellent opportunity to provide an update on the status of all aspects of the program as well as an opportunity to expand partnerships with other organizations.
For more information about NRSP-7, please visit our website http://www.nrsp-7.org or call Dr. Meg Oeller at (301) 827-3067.
Dr. Oeller is a Veterinary Medical Officer in CVM's Office of the Director.