US Food and Drug Administration: JanFeb

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FOOD AND DRUG ADMINISTRATION

U.S DEPARTMENT OF HEALTH AND HUMAN SERVICESPUBLIC HEALTH SERVICE

January/February 2002Vol. XVII, No. I

CENTER FOR VETERINARY MEDICINE

In This Issue

NRSP-7 Committee Meeting..... 2Surveying Feed Commoditiesfor Antibiotic Resistance ......... 6

Antimicrobials in Hatcheries .... 8CVM Establishes NewProject Management Staff ...... 11

STATEMENT BY HHS SECRETARY TOMMY G. THOMPSON

Regarding Release of Harvard BSE Risk Assessment

AHarvard University study releasedtoday has found that thanks to

the joint efforts of the Department ofHealth and Human Services and theDepartment of Agriculture, BovineSpongiform Encephalopathy (BSE)—or “Mad Cow Disease”—poses onlyan “extremely low” risk to our con-sumers and agriculture.

The study shows that even if thedisease should appear in the United

States, it would be contained by thesafeguards already put in place bythe Food and Drug Administrationand USDA. This is a reassuring find-ing, but it also means that we can-not let those safeguards down, andthat we must constantly keep improv-ing them.

Protecting our country against BSEhas been among my top concernssince I took my present post. One ofmy first initiatives was the launchingof an action plan to protect this coun-try against BSE.

Today, I want to join the Harvardresearchers in emphasizing the criti-cal importance of FDA rules that pro-tect our herds from BSE. As theHarvard study demonstrates, these

rules are a strong firewallagainst the spread of BSEin American herds.

Since these measureswere put in place in 1997,FDA has gone to greatlengths to impress on allrenderers, feed mills andsimilar establishments inthis country that theserules are vital for the

health of our consumers,agriculture, and eco-nomy. As part of the pro-gram, FDA and its state feed inspec-tor colleagues have developed aspecial guidance for the animal feedindustry, held public meetings withstakeholders, and conducted morethan 12,000 inspections and re-in-spections of the more than 10,000renderers and feed mills in the U.S.These inspections will continue.

Support for FDA’s measures hasbeen gratifying. Industry and govern-ment agree: American consumerscan and must be protected. Today, weare well on the way to achieving fullcompliance, and we must not settlefor less.

VMAC MEETING SCHEDULED FOR JANUARY 2002

The FDA Veterinary Medicine Ad-visory Committee (VMAC) will

meet on January 22, 23, and 24, 2002,

from 8:30 a.m. to 5 p.m., at theDoubleTree Hotel, Plaza Rooms I, II,

and III, 1750 Rockville Pike, Rockville,

MD. This FDA public advisory com-mittee meeting will be open to the

public. The general function of the

committee is to provide advice and

recommendations to the Agency onFDA’s regulatory issues. At the Janu-

ary meeting, VMAC will seek recom-

mendations on the issues of importtolerances under the provisions of

the Animal Drug Availability Act of

1996 (ADAA), and on the antimicro-bial drug effects on pathogen load in

food-producing animals as pathogen

load relates to the pre-approval proc-

ess of new animal drug applications(NADAs). Information concerning the

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There are still some components ofthe animal feed industry that are fail-ing to live up to the FDA standards. Iwant it to be clear that we intend toenforce FDA’s rules with increasedvigor.

FDA, USDA, and our state and pri-vate sector partners deserve to becongratulated on their performancein combating BSE. But we cannot reston our success to date. As theHarvard assessment makes clear,continued vigilance and concern areessential.

This statement was issued Friday,November 30, 2001.

FDA feed rules play a critical role in protecting our herds from BSE.

P h o t o b y S c o t t B a u er



January/February 2002FDA Veterinarian

2 VMAC MEETING SCHEDULED FOR JANUARY 2002 (Continued)

FDA Veterinarian

Bernard A. Schwetz, D.V.M. , Ph.D.

Acting Principal Deputy Commissioner of

Food and Drugs

Stephen F. Sundlof, D.V.M., Ph.D.

Director

Center for Veterinary Medicine

Karen A. Kandra, Editor

Published bi-monthly.

Home Page: http://www.fda.gov/cvm/

Articles are free of copyright and may be

printed.

Comments are invited.

Phone (301) 827-3800

FAX (301) 827-4065 or write to:

FDA Veterinarian (HFV-12)

7519 Standish Place

Rockville, MD 20855

discussion of import tolerances canbe found in an August 13, 2001 CVMUPDATE and in a Federal Register

notice of August 10, 2001.Information concerning the issues

of pathogen load will be made pub-licly available to the VMAC membersand the public in advance of themeeting and posted on CVM’s HomePage. A limited number of paper cop-ies of the background informationwill be available at the meeting.

Interested persons may presentdata, information, or views, orally orin writing, on the issues pending be-fore the committee. Written submis-sions may be made to Aleta Sindelar,Center for Veterinary Medicine (HFV-

3), Food and Drug Administration,7519 Standish Place, Rockville, MD20855. Written comments must besubmitted by January 4, 2002. Oralpresentations from the public will bescheduled between approximately1:30 p.m. and 4:15 p.m. on January22, and 8:45 a.m. and 11:00 a.m. onJanuary 24, 2002. The time allottedfor each presentation may be limited.Individuals wishing to make oral pre-sentations should notify AletaSindelar (telephone number 301-827-4515 or address above) before Janu-ary 4, 2002. They should submit abrief statement of the general natureof the evidence or arguments theywish to present, the names and ad-

dresses of proposed participants, andan indication of the approximate timerequested to make their presentation.They will be notified of their allottedtime prior to the meeting. Their en-tire statements should be submittedfor the record.

Additional information about theVMAC meeting will be included onthe FDA/Center for Veterinary Medi-cine Home Page. Up-to-date informa-tion on the VMAC meeting is alsoavailable on the FDA Advisory Com-mittee Information Line, 1-800-741-8138 (301-443-0572 in the Washing-ton, DC area), code 12546.

NRSP-7 HOLDS SEMI-ANNUAL COMMITTEE MEETING

The USDA’s Minor Use AnimalDrug Program, National Research

Support Project #7 (NRSP-7) held itssemi-annual meeting of the techni-cal committee and administrative ad-visors on October 22 and 23 inRockville, MD and Washington, DC.The spring meeting is hosted eachyear by one of the four regions, but

the fall meeting is always held in theWashington area to provide an oppor-tunity for input from members of FDA’sCenter for Veterinary Medicine (CVM).

The purpose of the NRSP-7 MinorUse Animal Drug Program is to ad-dress the shortage of minor use ani-mal drugs by funding and oversee-ing the efficacy, animal safety, andhuman food safety research and en-vironmental assessment required fordrug approval. The scope of the pro-gram includes minor species of agri-

cultural importance, and generallyexcludes companion animals.

Attendance

The technical committee is madeup of a National Coordinator, 4 Re-gional Coordinators, 4 Regional Ad-ministrative Advisors, and liaisonsfrom USDA and FDA. The NationalCoordinator is Dr. John Babish(Cornell University). The RegionalCoordinators are Dr. Arthur Craigmill

by Meg Oeller, D.V.M.

(University of California, Davis), Dr.Alistair Webb (University of Florida),Dr. Robert Holland (Iowa State Uni-versity), and Dr. Paul Bowser (CornellUniversity). The Administrative Advi-sors are Dr. Kirklyn Kerr (Universityof Connecticut), Dr. John Nielson(University of Florida), Dr. DavidThawley (University of Nevada), and

Dr. Don Robertson (Kansas StateUniversity). The USDA representativeis Dr. Larry Miller (Washington, DC)and the FDA liaison is Dr. Meg Oeller(Rockville, MD). This meeting wasalso attended by the National NADAcoordinator for Aquaculture, Rosalie“Roz” Schnick and Dr. MarkFeldlaufer of the USDA Bee lab inBeltsville, MD, as well as by review-ers and managers from FDA/CVM.

This meeting was postponed fromits originally scheduled dates in Sep-

tember due to the upheaval in travelarrangements following September11. Because of the change, three ofthe four administrative advisors wereunable to attend. Dr. Don Robertsonwas their sole representative at thismeeting.

Welcoming Remarks From Dr.

Sundlof

The Director of CVM, Dr. StephenSundlof, welcomed everyone and

explained that the coming year looksvery promising for the Center with aproposed budget increase. Hepointed out that CVM was still work-ing under a continuing resolutionpending passage of the budget. In thenext year, a high priority will be on-farm and feed mill inspections basedon Bovine Spongiform Encephalopa-

thy (Mad Cow) concerns.Strategic planning at CVM is start-

ing again with an emphasis on “backto basics”. Some items of special in-terest include controlling internet




FDA Veterinarian January/February 2002

NRSP-7 HOLDS SEMI-ANNUAL COMMITTEE MEETING (Continued)

pharmacies, reduction of the applica-tion backlog through the use of con-

sultants to find efficiencies, and thedevelopment of tolerances & testingfor residues in imported foodstuffs.

A contract has been awarded to ICFConsulting to identify medicationsused in aquaculture around the

world. The U.S. is concerned abouta competitive disadvantage com-pared to overseas producers, espe-

cially in the case of seafood fromSoutheast Asia. Some of this may becorrected by the requirement for ex-

porters to have Hazard Analysis Criti-cal Control Point (HACCP) plans inplace, since such plans require dis-

closure of medications used onfarmed fish.

Antimicrobial resistance develop-ment remains a major concern. Anew guidance document is plannedfor publication in the Spring. Dr.

Sundlof noted that there are stillproblems enforcing prudent use ofantibiotics. Links are being estab-

lished with State veterinary boardsto assist with enforcement in the ar-eas of prudent use of antibiotics,

compounding, and catalog sales. Dr.Sundlof also said that CVM has re-ceived a special allotment of $3 mil-

lion for studies on subtherapeuticdrug use. He was questioned aboutthe advisability of NRSP-7 pursuing

a project for florfenicol in sheep. Heanswered that antimicrobial resis-

tance requirements should not besufficient to discourage such aproject.

National Coordinator’s Report

Dr. Babish reported on his meetingwith the North Eastern Experimental

Station Directors. He was encouragedto make visits to other regions to

make sure they are aware of the pro-gram. The Southern region will needspecial attention as they face the fu-ture retirement of AdministrativeAdvisor John Neilson and select hisreplacement.

The new NRSP-7 brochures havebeen printed but the web site addresswas inadvertently omitted. A labelwith the address will be affixed to the

brochure before they are distributed.The brochure includes a descriptionof the program’s mission, back-ground, and organization as well asa list of the contact information forthe members of the technical com-mittee and administrative advisors.On the back of the brochure is anabbreviated Animal Drug Requestform so that interested persons maysuggest new projects for the programto pursue.

Administrative Advisors’

Report

Dr. Don Robertson said that JohnBabish sent NRSP-7 update letters tomajor stakeholders in the sheep, goat,gamebird, and aquaculture industries.

He advised that we should make aneffort to maintain and expand such re-lationships.

USDA Representative’s Report

Dr. Miller related that the USDAbudget is on hold. The House bud-get is the same as last year but theSenate shows an increase. He de-scribed the plan for the next day’smeeting with administrators at USDAand the order of presentations thatwe should give.

Regional Coordinators’ Reports

N ORTHEAST R EGION : Dr. Paul Bowser.

Although many of these projectsare intended to support speciesgrouping, the data will be accumu-lated to support individual drug ap-provals for the drugs under study.Current projects include hydrogenperoxide for bacterial gilldisease in finfish, oxytet-racycline for finfish, sulfa-

dimethoxine/ormetoprim(Romet-30TM) for finfishand sulfadimethoxine/ ormetoprim (RofenaidTM)for pheasants.

S OUTHERN R EGION : Dr.Alistair Webb

Dr. Webb reported thatcurrent projects includeivermectin for rabbits,fenbendazole for deer,

lasalocid for deer and goats,fenbendazole, nitarsone, and zoalenefor gamebirds, and carp pituitary ex-tract for fish.

Most discussion centered on Dr.Kelly’s (Mississippi State University)proposal to complete the carp pitu-

itary extract target animal safetywork. Dr. Kelly proposed both exten-sion of species covered as well as anextensive list of tissues for histopa-thology. NRSP-7 has provided admin-istrative assistance, but has not

funded this work previously. The con-sensus at the meeting was that it is aneeded production tool and shouldbe supported.

N ORTH C ENTRAL R EGION : Dr. Robert

HollandThe major current project is the

CIDR-G intravaginal progesteronedevice for sheep. There have beennumerous complications of theproject resulting from the sale of thedevice from the original New Zealandmanufacturer. We hope to resolvethese problems so that this approvalcan be pursued. The U.S. sheep in-dustry lists this product as its num-ber one need.

W ESTERN R EGION : Dr. Arthur Craigmill

Dr. Craigmill reported on severalcompleted and inactivated projects.Those completed include a pharma-cokinetic study for ceftiofur in alpacasand llamas and another on pharma-cokinetics and residue depletion ofoxytetracycline in sheep.

P h o t o b y S c

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4

Current projects include ivermectinpour-on for bison, strontium chloridein salmonids, and pirlimycin for dairygoats. The bee projects were dis-cussed later by Dr. Feldlaufer. Somespecies grouping work is underwayin gamebirds.

New Projects

NORTHEAST REGION – A new project isplanned for goats, although the de-tails are not yet determined.

SOUTHERN REGION – A new projectwith imidocarb for babesiosis incattle is projected, but not certainpending sponsor agreement.

NORTH CENTRAL REGION – Three newprojects have been proposed. Final

decisions are pending additional in-formation. The proposed projects arefor Apitol for bees to treat varroamites, florfenicol for mycoplasma in-fections in veal calves, and a treat-ment for mastitis in ewes.

WESTERN REGION – A new project willbe started in the coming year forflorfenicol in sheep & goats for bac-terial respiratory infections and pos-sibly also for a foot rot claim.

Other Reports

Dr. Mark Feldlaufer of the USDAbee lab in Beltsville discussed hiswork in support of New Animal DrugApplications for lincomycin and ty-losin for American foulbrood in hon-eybees. The target animal safetystudy data have been submitted, theresidue depletion studies are done,and effectiveness studies are under-way. Dr. Oeller has obtained lettersfrom CVM agreeing that antimicrobialresistance studies will not be needed

for these projects. The environmen-tal assessments are in progress.

Roz Schnick distributed her hand-out, “Update on the Activities of theNational Coordinator for AquacultureNew Animal Drug Applications.” Shedescribed the progress of the activeprojects of the Federal-State Aqua-culture Drug Approval PartnershipProject. These projects include claimsfor Aqui-STM (anesthetic), Chlora-mine-T, Copper Sulfate, Florfenicol,

hydrogen peroxide, and oxytetracy-cline. This group is also conductingstudies to support species grouping.

FDA’S NRSP-7 Liaison Report

The Minor Use/Minor Species Ani-mal Health Act of 2001 (the MUMSBill) has been introduced in bothhouses of Congress and is continu-ing to add co-sponsors. If

enacted, this legislationwould make incentivesavailable to pharmaceuti-cal sponsors, allow forconditional approvals ofMUMS drugs, and allowlegal marketing of someproducts for non-food-producing animals underan indexing system.

Current projects werereviewed and some were

reclassified as ‘inactive’ for the timebeing. The committee discussed Inves-tigational New Animal Drug (INAD) in-vestigators who are not producing orsubmitting their data. In some cases,producers/collaborators might moreappropriately get the drugs under thenew Compliance Policy Guide on

Active NRSP-7 Projects

Drug Route of Species Indication Region Administration

IVERMECTIN ....................... injection rabbits ear mites S

TYLOSIN ............................ soluble powder honey bees American foulbrood W

LASALOCID ........................ oral (feed) pheasant coccidiosis S

TILMICOSIN ....................... injection veal calves respiratory infections NC

PROGESTERONE ................. CIDR sheep estrus synchronization NC

HYDROGEN PEROXIDE ... ...... topical var ious f ish bacterial gill disease NE

CARP PITUITARY ................ injection various fish spawning aid S

SULFADIMETHOXINE / ORMETOPRIM . .. .. .. ... .. .. .. .. .. oral (feed) pheasants bacterial infections NE

and coccidiosis

NITARSONE ........................ oral (feed) partridge blackhead S

ZOAMIX ............................. oral (feed) pheasants coccidiosis S

FENBENDAZOLE .................. oral (feed) pheasants, gapeworm, capillaria Spartridges &quail

OXYTETRACYCLINE ............. oral (feed) finfish bacterial infections NE

LASALOCID ........................ oral (feed) deer coccidiosis S

STRONTIUM CHLORIDE ....... immersion finfish otolith marking W

LASALOCID ........................ oral (feed) goats coccidiosis S

PIRLIMYCIN ....................... intramammary goats mastitis W

LINCOMYCIN ...................... soluble powder honey bees American foulbrood W

SULFADIMETHOXINE /

ORMETOPRIM .................... Oral (feed) f infish Bacter ial infections NE

P h o t o b yP e g g y Gr e b






extralabel use of drugs in feed forminor species (CPG 615.115).Those groups should either con-tinue to submit effectivenessdata whenever they use thedrug under the INAD, or theyshould use the CPG to acquireneeded medicated feeds. Othergroups that are studying drugsunder an NRSP-7 INAD and notsubmitting data at all must eithersubmit the data as promised, orhave the INAD file inactivated.

It is important that NRSP-7 follow therules that allow unapproved uses ofthese drugs under its INADs. It is im-perative that this data, including No-tice of Claimed Investigational Exemp-tion forms, be submitted in a timely

manner so that inspections can bescheduled, and slaughter authoriza-tions can be kept up to date. CVM cantake regulatory action against sponsorsand investigators who fail to complywith these requirements. NRSP-7 mustadminister its INAD files in full compli-ance with the laws and regulations.

Species Grouping

This concept involves demonstrat-ing, usually through pharmacokinet-ics, that similar species may be

grouped for the purposes of demon-strating effectiveness, target animalsafety, and human food safety. Oneoutcome may be that a representa-tive species can be studied to providedata to support the inclusion of simi-lar species on the label of a new ani-mal drug. This is probably mostneeded in aquaculture where thereare literally hundreds of species andit is not practical to test the drug onthem all. Other groups also couldbenefit from such research. This in-

cludes gamebirds (pheasants, par-tridges, and quail), deer (white tail, reddeer, elk, etc.), and ratites (ostriches,emus, and rheas). It may be that theresearch will show that the species arenot similar, or are not similar for someclasses of drugs. Learning what is andis not suitable for grouping will be veryvaluable in making drug approval forminor species more efficient.

Dr. Renate Reimschuessel ex-plained the CVM’s Office of Research

strategy in the pursuit of rational spe-cies grouping. They are studyingmultiple species (trout, tilapia, cat-fish, yellow perch, toadfish, salmon);under varying conditions (warm &cold/fresh & sea water); using mul-tiple drugs (albendazole, ivermectin,

flumequine). They are looking at druglevels in muscle. Badaruddin Shaikhpresented data for albendazole in troutand tilapia (the sulfoxide and sulfoneare the metabolites measured).

Dr. John Babish also discussed hisspecies grouping approach. He is look-ing at characterizing species by drugmetabolism ability with emphasis onP450 & CYP families. He is character-izing these with western blot & enzy-matic analysis. The fish species heand Dr. Bowser are studying are rain-

bow trout, tilapia, walleye, yellowperch, summer flounder, hybrid stripedbass, and channel catfish. The humanbased enzyme antibody assays cross-react with fish and gamebirds (quail).

GLP Discussion

This discussion centered on inspec-tions and the mechanism of a dataaudit. Dr. Lynn Friedlander, of CVM,explained the requirements for in-spections, mechanisms for data au-dits, and information that should be

included in human food safety datasubmissions. It was a very useful dis-cussion.

Spring 2002 Meeting

The Spring meeting of the NRSP-7Technical Committee and Administra-tive Advisors will be held in Davis,California on April 29 and 30, 2002.There will be a tour of the University’ssheep dairy followed by the businessmeeting.


DAY TWO

The second day of the meet-ing was held at the USDA Wa-terfront Offices. This meetingwas attended by the NRSP-7members and Roz Schnick.

Midmorning, the group wasjoined by USDA administrators.

International Workshop

The NRSP-7 program tradi-tionally hosted a workshop on

a minor species concern every 2years. The last workshop was held in1996 on the topic of “Drug Approvalfor Minor Species in the 21st Cen-tury”. After 1996, resources were di-rected toward activities other thanthe sponsorship of workshops. The

program planned to hold a workshopnext September or October at a ho-tel in the Dulles airport area.

The committee decided to postponethe workshop until September 2003 inview of overseas travel fears. Dr. Webband Dr. Craigmill are co-chairing themeeting. They circulated a draft pro-gram outline. The current plan is tohave the workshop center on interna-tional issues for minor species andminor uses. The meeting will be heldin cooperation with Global FARAD (the

Food Animal Residue Avoidance Data-bank). The committee will investigateholding the workshop in Baltimore.

Meeting with USDA

Administrators

The group then met with GaryCunningham, Ted Wilson, BillWagner, Gary Jensen, and Dave Morrisof USDA. Several members of thecommittee gave presentations on theNRSP-7 program, including, back-ground on the program, species

grouping efforts, species projectsummaries, and the role of FDA/CVM.A productive discussion followed.

NRSP-7 Website

Dr. Webb provided an overview ofthe new and improved NRSP-7website: http://www.nrsp7.org . Thewebsite currently provides links tominor species group websites,updated names and addresses of

P h o t o b y J a c k D yk i n g a

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6 SURVEYING FEED COMMODITIES FOR ANTIBIOTIC RESISTANCE

Widespread dissemination of re-sistance to antibiotics resulting

from the selective effect of drug usein food animals may have importantramifications for both human andanimal health. A critical question rel-

evant to this ecological issue is: Whatis the source of the resistance deter-minants? Are they always present inthe environment at low, virtually un-detectable levels or are they introducedfrom outside? Are there managementpractices that could minimize or elimi-nate resistance development? Answersto these questions could lead to im-provements in our ability to controldevelopment and dissemination ofresistance to antibiotics and therebyoptimize their efficacy, extend their

useful lifespan, and minimize pos-sible negative health consequences.

Animal feeds and feed commodi-ties may serve as vectors for the dis-semination and maintenance of resis-tance determinants in the animalproduction environment and therebyin the food supply. The commercialfeed industry, during 2000, suppliedan estimated 119 million tons of feedthat were required to support inten-sive integrated animal production inthe United States. This figure does

not include the millions of tons offeed mixed on farms. With the excep-tion of the cereal grains and grasses,virtually all other commodities thatcomprise animal feeds are by-prod-ucts of other industries including theanimal production industry. The ren-

by David Wagner, Ph.D.

dering industry reported the produc-tion of 8.8 billion pounds of proteinmeals in 2000. A large portion ofthese products is incorporated intoanimal feeds. It is therefore not unrea-sonable to view the feed industry as a

recycling business that utilizes by-prod-ucts of high nutritional value fromother industries, to provide complexnutrient sources for animal production.

Recently, the issue of antibiotic re-sistance resulting from the use ofantibiotics in animal production hasonce again become a significant con-cern to the Center for VeterinaryMedicine (CVM) and other nationaland international health agencies.The potential for resistance develop-ment in animal production settings to

negatively impact human therapeuticefficacy is being revisited. The role thatfeed may play in the dynamics of anti-biotic resistance development and dis-semination in the animal productionenvironment is essentially unknown.The possibility that feed may serve notonly as a vector for resistance but alsomay function to maintain and concen-trate resistance due to its recyclingcharacteristic may be important. Thereare essentially no data available to as-sess the potential role of animal feed

to serve as a vector for the transmis-sion and/or maintenance of antibioticresistant bacteria or resistance deter-minants in the animal environment.

During FY 2000, CVM’s Division ofAnimal and Food Microbiology initi-ated a preliminary survey of animal

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NRSP-7 HOLDS SEMI-ANNUAL COMMITTEEMEETING (Continued)

committee members, interactive Ani-mal Drug Request Forms for newproject requests, and a “FrequentlyAsked Questions” section. Plans areunderway to implement features in-cluding “Breaking News”, featurearticles, a searchable database ofanimal drugs, and a searchable da-tabase of NRSP-7 activities. Pleasevisit the site.

The day-and-a-half meeting was anexcellent opportunity to provide an

update on the status of all aspects ofthe program as well as an opportu-nity to expand partnerships withother organizations.

For more information about NRSP-7, please visit our website http://

www.nrsp7.org or call Dr. Meg Oellerat (301) 827-3067.

Dr. Oeller is a Veterinary Medical

Officer in CVM’s Office of the Director.

feed commodities to assess their rolein antibiotic resistance dissemination.Poultry by-product meal, meat andbone meal, blended animal proteins,and whole cereal grains (corn and oats)were the first products cultured. En-

terococcus spp. were isolated, iden-tified to species, and tested for sus-ceptibilities to 17 antibiotics using abroth microdilution assay. The anti-biotics are incorporated in a custom-ized Gram positive panel that is usedin the National Antimicrobial Resis-tance Monitoring System (NARMS)and produced by TREK Diagnostics,Inc. Eleven of the antibiotics are ei-ther used directly in the feed or wa-ter of animals or they are membersof drug classes used in these ways.

A total of 175 samples were cul-tured. All were positive for entero-cocci except for corn (41%, 24/58) andpoultry meal (95%, 19/20). Enterococ- cus faecium was by far the mostprevalent Enterococcus species, ac-counting for 72% (167/232) of the iso-lates recovered. Enterococcus faecalis was rarely recovered fromany of the samples tested. Nine of thetwelve isolates recovered came fromcorn. This is interesting because E.faecalis is the most common cause

of human infections accounting formore than 80% of reported cases. Itis also the species most commonlyisolated from animal production en-vironments and from the intestinalcontents of animals including hu-mans. All of the samples of oats werepositive for enterococci (36) but noE. faecalis were isolated. The resultsthus far show that enterococci arewidely disseminated in the environ-ment and can readily be isolatedfrom feed commodities.

Resistance to antibiotics used inhuman therapy was primarily seen inisolates recovered from meat andbone meal and was observed for tet-racycline, streptomycin, and erythro-mycin. Reduced susceptibilities toantibiotics used only in animal pro-duction were observed in significantproportions of the isolates from all therendered animal by-products testedespecially bacitracin susceptibility.




Resistance to ciprofloxacin was de-tected, but only in the isolates recov-ered from the cereal grains. None ofthe 167 isolates of Enterococcus faeci- umwere determined to have minimuminhibitory concentrations (MIC) forSynercid above the NCCLS breakpointof 4 ug/ml. This observation stands instark contrast to E. faecium isolates re-covered from litter taken from poultryproduction houses where about 65%of E. faecium are resistant to Synercidat concentrations up to 32ug/ml. Thisdifference between feed and produc-tion environmental isolates probablydemonstrates the selective effect elic-ited by virginiamycin use in feed. Noresistance to Linezolid or penicillin,drugs of critical importance to humantherapy was observed in any of thefeed isolates tested.

What seems to be most remarkableabout the data collected to date is thelimited amount of antibiotic resis-tance associated with isolates fromfeed commodities relative to thatseen in animal production environ-ments. For example, Enterococcus isolates from poultry by-productmeal are very susceptible to drugssuch as penicillin and Synercid;

whereas, isolates recovered frompoultry production houses are veryresistant with 75% and 65% of theisolates being resistant to the twodrugs respectively. One question ofinterest resulting from these data is:Why are the isolates associated withpoultry meal not resistant when thosefrom live poultry are? The apparentdecrease in susceptibility of isolatesrecovered from feed to the commonlyused production drugs bacitracin, ty-losin, and lincomycin may be an is-sue of concern to animal production.

This survey activity is continuingand will be expanded during 2002with the involvement of the FDA’sOffice of Regulatory Affairs whichwill conduct a national sampling pro-gram of rendered feed commodities.These samples will be submitted toCVM’s Office of Research for cultur-ing and analysis. In addition to En-

terococcus , E. coli, salmonellae, andCampylobacter will be selectively cul-tured and tested for antibiotic sus-ceptibility profiles.

Dr. Wagner is a Research Animal

Scientist in CVM’s Division of Animal and Food Microbiology.

SURVEYING FEED COMMODITIES FORANTIBIOTIC RESISTANCE (Continued)

COMMENT PERIODEXTENDED FORIMPORT TOLERANCESANPRM

The Food and Drug Administration(FDA) is extending to March 11,

2002, the comment period for the

advance notice of proposedrulemaking (ANPRM) that appearedin the August 10, 2001, Federal Reg-

ister . The ANPRM stated that FDA in-tends to propose a regulation for es-tablishing import tolerances, andsolicited comments on issues relatedto the implementation of the importtolerances provision in section 4 ofthe Animal Drug Availability Act of1996 (ADAA). The ADAA authorizesFDA to establish drug residue toler-ances (import tolerances) for im-

ported food products of animal ori-gin for drugs that are used in othercountries, but that are unapprovednew animal drugs in the U.S. Foodproducts of animal origin that are incompliance with the import tolerancewill not be considered adulteratedunder the Federal Food, Drug, andCosmetic Act and may be importedinto the United States. FDA is extend-ing the comment period to providestakeholders sufficient opportunity to

comment at the January 22-24, 2002,public advisory committee meetingand within sixty days thereafter.

Written or electronic comments onthe ANPRM should be submitted to theDockets Management Branch (HFA-305), Food and Drug Administration,5630 Fishers Lane, Room 1061,Rockville, MD 20852, by March 11,2002. Electronic comments should besubmitted to http://www.fda.gov/

dockets/ecomments . Commentsshould reference Docket No. 01N-0284.

Additional information on theANPRM is included in the August 10and December 7, 2001, Federal Reg-

ister (http://www.fda.gov/OHRMS/

DOCKETS/98fr/081001a.htm andhttp://www.fda.gov/OHRMS/DOCK-

ETS/98fr/120701c.htm,) and fromFrances Pell, Center for VeterinaryMedicine (HFV-235), Food and DrugAdministration, 7500 Standish Place,Rockville, MD 20855, 301-827-0188, E-mail: [email protected].

CVM is pleased to announce thatDr. Merton V. Smith has been se-

lected to fill the position as SpecialAssistant for International Activities,Office of the Director, CVM.

Dr. Smith comes from FDA’s Officeof International Programs (OIP) in theOffice of the Commissioner. For thepast 16 years, Dr. Smith has held anumber of positions in OIP and itspredecessor unit, the InternationalAffairs Staff, including the Africa andNear East Desk Officer, the AmericasDesk Officer, the Multilateral Pro-grams Desk Officer, and the Interna-tional Harmonization and Trade Af-fairs Desk Officer. Most recently, hehas been the Acting Director, Inter-national Agreements Staff, OIP.

Dr. Smith was detailed to the Of-fice of the U.S. Trade Representative

in the Executive Office of the Presi-dent for a year (’93-’94) and workedto finalize both the North AmericanFree Trade Agreement and the Uru-guay Round of Multilateral TradeNegotiations, the latter establishingthe World Trade Organization.

Dr. Smith received his B. A. degreefrom the University of Virginia, andM. S. and Ph.D. degrees in food sci-ence and nutrition from Virginia Poly-technic Institute, completing researchin the area of food-borne infectionsand intoxications. He also receivedhis J. D. degree at Catholic Univer-sity, focusing on environmental,trade, and administrative law. Dr.Smith is currently a member of theDistrict of Columbia Bar. He may bereached at 301-827-6239.

NEW CVM OFFICIAL FOR INTERNATIONALACTIVITIES




8

Recently, the Centers for Disease

Control and Prevention (CDC) re-

ported the emergence of domesti-

cally acquired ceftriaxone-resistant

Salmonella in humans in the U.S.

This antimicrobial resistance wasdetected by the routine surveillance

of the National Antimicrobial Resis-

tance Monitoring System (NARMS).

Because ceftriaxone-resistant Salmo-

nella has become a public health con-

cern, the Center for Veterinary Medi-

cine (CVM) Office of Surveillance and

Compliance issued a high priority

assignment directed at identifying

the use of ceftiofur and other antimi-

crobial drugs in a nationally repre-

sentative sample of poultry hatcher-ies in the United States.

Historically, populations of bacte-

ria have impacted human and animal

health, without facing much of a chal-

lenge to their own well-being. That

situation changed in the early 1940’s,

as antimicrobial drugs, the first sig-

nificant weapons in the fight against

bacterial illnesses, were widely mar-

keted. While antimicrobial drugs

have been an extremely effective

treatment, over time, bacteria that are

resistant to antimicrobial drugs have

emerged.

Today, almost all bacteria that were

universally susceptible to antibiotics

are now resistant to at least some of

these drugs, and some bacteria are

resistant to many different antibiot-

ics.1 Selective pressure exerted by

antimicrobial drug use can result in

the development of antimicrobial re-

sistance.2 The use of antimicrobials

in human medicine as well as in food

animal production may promote thistype of selection.

Antimicrobial drugs are used in

animal agriculture to treat disease, to

prevent disease, and to promote

growth/feed efficiency. While it is

known that the administration of an-

timicrobials to food animals can se-

lect for resistance among bacteria

which may subsequently be passed

to humans through the consumption

of food or by direct contact, the ex-

act magnitude of the human health

impact has been difficult to quantify.3

Some human bacterial infections ac-

quired from food animal sources may

not respond to antimicrobial drugschosen for treatment because a simi-

lar drug was given to the food ani-

mal and resulted in the development

of resistant organisms.

Approximately 1.4 million cases of

salmonellosis occur in the U.S. each

year, most in children and the elderly,

and an estimated 600 of these cases

are fatal.4 Ceftriaxone, a third genera-

tion cephalosporin, is the drug of

choice for treating invasive Salmo-

nella infections. Resistance to thisdrug is a concern, particularly in chil-

dren, since fluoroquinolones, an al-

ternative treatment, are not approved

for use in children.4

Because of cross-resistance be-

tween the veterinary drug ceftiofur

and the human drug ceftriaxone, and

because food animals are the pre-

dominant source of domestically ac-

quired Salmonella infections,

ceftiofur use may be contributing to

ceftriaxone-resistant Salmonella

which are subsequently acquired by

people via food consumption or by

direct contact. Ceftiofur is the only

expanded spectrum cephalosporin

drug approved for systemic use in

food animals in the U.S. This drug is

currently approved for therapeutic

use in cattle, swine and poultry. The

majority of cephalosporin-resistant

Salmonella express an extended-

spectrum -lactamase, which is able

to hydrolyze oxyimino cephalospor-

ins and monobactams, but not thecephamycins. However, recent re-

ports indicate that several organisms

of Enterobacteriaceae have obtained

plasmids encoding AmpC-like-lac-

tamases that hydrolyze the cepha-

losporins as well as the cephamycins

such as cefoxitin and ceftriaxone.

Resistance to ceftriaxone and ceftio-

fur is mediated by a cephalomy-

cinase (CMY) encoded by the bla CMY

gene, and eleven bla CMY

variants have

been described to date. Recent re-

search conducted in the Office of Re-

search at CVM identified plasmid-

mediated AmpC-like-lactamases in E.

coli and Salmonella isolated fromfood animals and retail meats. These

bla CMY

genes were further shown to

be transferred between different bac-

teria.5

The Assignment Memorandum in-

cluded a six-page questionnaire to

identify hatchery compliance with 21

CFR Part 530, which addresses

extralabel drug use in animals.

Extralabel drug use is legal if require-

ments in the regulation are satisfied

(e.g., use of the drug by or on thelawful order of a licensed veterinar-

ian within the context of a valid vet-

erinary-client-patient relationship).

Prior notice was not given to person-

nel at inspected sites. The Assign-

ment Memorandum, which was sent

to District Directors, Directors of In-

vestigation Branches, and FDA Dis-

trict Offices, required the following

actions: Inspection of the hatchery to

determine compliance with 21 CFR

530, completion of all inspections

during FY01, coordination of follow-

ups by Districts so that as many vis-

its as possible could be conducted on

the same day and collaboration with

CVM so that a representative from

the Division of Epidemiology could

work with Field Personnel during

each inspection. Directions to Field

Personnel included: 1) Review all

medication/treatment records to

identify antimicrobials used by the

firm, 2) Review labels on the drugs

found at each site to ensure that useis per approved label directions, and

3) Evaluate any extralabel use to de-

termine if the drug was prescribed by

a veterinarian within the context of a

valid veterinary-client-patient rela-

tionship and satisfied other require-

ments of 21 CFR Part 530.

The hatcheries inspected were ran-

domly selected in an effort to focus

USE OF ANTIMICROBIALS IN HATCHERIES: A FIELD ASSIGNMENT


by Linda E. Silvers, D.V.M., M.P.H. and Charlotte D. Spires, D.V.M., M.P.H., D.A.C.V.P.M.




on use patterns that are representa-

tive of most poultry hatcheries in the

U.S. Epidemiologists and microbiolo-

gists from CVM’s Division of Epide-

miology collaborated with local FDA

field investigators as well as withmembers of CVM’s Division of Com-

pliance to inspect 37 chicken and tur-

key hatcheries. The size of the hatch-

eries and the types of operations

varied. A questionnaire that captured

use information for ceftiofur and

other antimicrobials such as gentami-

cin (an aminoglycoside antimicrobial

drug approved for use in poultry),

was administered, and a site inspec-

tion was conducted at each hatchery.

Data collected included demographicinformation, current and past

ceftiofur and gentamicin usage,

routes of administration, doses ad-

ministered, number of chicks or

poults produced at the facility and the

proportion of chicks or poults treated

with the antimicrobial drug.

Biosecurity suits, hats and shoe

covers were necessary in several

hatcheries. In most instances, the

hatcheries supplied the inspectors

with all of the necessary items that

were needed to meet their

biosecurity requirements. These

ranged from no precautions to

shower in-shower out facilities.

On September 11th, when the ter-

rorism attacks occurred, six Division

of Epidemiology members were in

travel status due to this field assign-

ment. As a consequence, several

travel itineraries were affected. This

disruption necessitated extension of

the assignment beyond the FY01

deadline for completion.Generally, interviewees from the

various hatcheries were very coop-

erative and provided all of the infor-

mation that was requested. Some

hatcheries were not inspected for

various reasons. In some instances,

the hatcheries were no longer opera-

tional. In one instance, the hatchery

USE OF ANTIMICROBIALS IN HATCHERIES: AFIELD ASSIGNMENT (Continued)

was at a university research facility

which only raised chicks for research

purposes. When possible, alternate

hatcheries in the area were identified.

A total of 27 commercial hatcheries

(22 chicken, 4 turkey, 1 combination)were actually inspected. The data is

currently being compiled and ana-

lyzed.

References

1. Levy SB. The antibiotic paradox.

New York: New York; 1992.

2. American Society of Microbiol-

ogy. Report of the ASM Task Force

on Antimicrobial Resistance.

Washington, DC March 1995.

3. Smith KE, Bender JB, Osterholm

MT. Antimicrobial resistance in

animals and relevance to human

infections. In: Nachamkin I, Blaser

MJ, editors. Campylobacter . 2nd

ed.Washington, DC: ASM Press;

2000. P.483-138.

4. Fey PD, Safranek TJ, Rupp ME,

Dunne EF, Ribot E, Iwen PC,

Bradford PA, Angulo FJ Hinrichs

SH. Ceftriaxone-resistant Salmo- nella infection acquired by a child

from cattle. New England Journal

of Medicine 2000;342(7):1242-

1249.

5. Zhao S, White GD, McDermott FP,

Friedman S, English L, Ayers S,

Meng J, Maurer JJ, Holland R,

Walker DR. Identification and Ex-

pression of Cephamycinase bla CMY

Genes in Escherichia coli and Sal-

monella Isolated from Food Ani-

mals and Ground Meat. 2001.Antimicrob. Agents Chemother.

45: 3647-3650.

Dr. Silvers is a Veterinary Medical

Officer in CVM’s Division of Epidemi-

ology. Dr. Spires is an Epidemiologist

in CVM’s Division of Epidemiology.

CVM SCIENTISTSATTENDCONFERENCE ONTRANSGENICANIMALS

by Wendelyn Warren, Ph.D. and KevinGreenlees, Ph.D., DABT

Seven scientists from the Office ofNew Animal Drug Evaluation and

the Office of Surveillance and Com-

pliance attended the Transgenic Ani-

mal Research Conference III. The con-

ference was held from September 9

through September 13, 2001 at the

Granlibakken Conference Center in

Tahoe City, California and was hosted

by the University of California at

Davis. This was the third in a series

of conferences since 1997 that

uniquely focuses on genetic engi-neering in animal species used in

agriculture. It was an international

meeting intended to bring together

researchers from the leading labora-

tories doing cutting edge research

and development with transgenic

animals.

The CVM attendees are all part of

the Animal Biotechnology Working

Group or the Biotechnology ProcessGroup. These groups identify and

resolve regulatory policy and scien-

tific issues regarding transgenic ani-mals. The presentations addressed

cutting-edge methodology, technical

improvements, and current progress

towards producing transgenic ani-

mals for medical, agricultural, and

even industrial applications. Informa-

tion was provided on basic and ap-

plied research through presentations,

posters, and informal discussions.CVM scientists were very interested

in understanding the advances in

genetic engineering and how theymay impact considerations of safety

and effectiveness, particularly in food

animals.

The field of transgenic animal re-

search is rapidly evolving towards

practical applications for this technol-ogy. Presentations ranged from dis-

cussion on how to spin spider silk

produced in the mammary gland of





10

The Food and Drug Administration(FDA) is announcing the availabil-

ity of a draft guidance for industry(#142) entitled “Pharmacovigilance ofVeterinary Medicinal Products: Man-agement of Periodic Summary Up-date Reports (PSUs).” This draft guid-ance has been developed by the

International Cooperation on Harmo-nisation of Technical Requirementsfor Registration of Veterinary Medici-nal Products (VICH). It is intended todescribe the reporting system foridentification of possible adverseevents following the use of marketedveterinary medicinal products sub-mitted to the European Union, Japan,and the United States.

Draft guidance #142 is available onthe FDA/Center for Veterinary Medi-

bioengineered goats to pharmaceu-tical production in the semen oftransgenic pigs, to the production oflow phosphorus manure inbioengineered pigs. Each of these

very different applications of bioengi-neering technology share the keystep of altering the structure andfunction of the bioengineered animal.Information about this conference isavailable through the University ofCalifornia at Davis web site at http:// www.biotech.ucdavis.edu/events/ events.htm.

Altering the structure and functionof an animal through the insertion ofthe transgenic material, and in somecases, the resulting expression prod-

uct are considered to be subject toFDA’s regulatory authority likely torequire the submission of a new ani-mal drug application to the Center forVeterinary Medicine (see Office ofScience and Technology Policy, Cen-ter for Environmental Quality CaseStudies of Environmental Regulationfor Biotechnology, http://www.ostp.gov/html/012201.html). Other FDACenters may have a role in the regu-lation of this new technology. The

FDA’s Center for Biologics, for ex-ample, regulates products such ashuman serum albumin or insulin in-tended for use in human medicineand harvested from the milk, semen,

or other tissue of the bioengineeredanimal.Because of the small size of the

conference, the nature of the setting,and the collegial atmosphere someof the most important stakeholderoutreach occurred over meals andcoffee breaks. CVM scientists dis-cussed the INAD and NADA processwith sponsors and potential sponsorsin this informal setting. There wasalso an opportunity for candid discus-sions with regulatory scientists from

Health Canada and the CanadianFood Inspection Service. The confer-ence allowed the CVM scientists toexpand their breadth of knowledgein this fast-growing field and to in-teract with potential stakeholders andother government’s agencies as thetools of genetic engineering find theirway into commercial applications.

The 2001 Transgenic Animal Con-ference was impacted by the terror-ist attacks on September 11, 2001.

The shock and grief caused by theseattacks was apparent in the discus-sions among the participants of theconference. Many attendees experi-enced considerable hardships in re-

turning home. Travel arrangementswere cancelled, rescheduled, and re-scheduled again as airports struggledto cope with the events. Althoughthoughts were with all those whohave been affected by this tragedy,it was clear that the conference so-lidified into a community of scientiststhat ignored national boundaries andbrought together the individuals fromacademia, industry, and government.We thank the conference organizersand the Granlibakken Conference

Center for their gracious understand-ing and support in a very difficulttime. We would also like to acknowl-edge the remarkable support andsolidarity expressed by the interna-tional attendees.

Dr. Warren is a Pharmacologist in the

Residue Chemistry Team in CVM’s Of-

fice of New Animal Drug Evaluation

(ONADE). Dr. Greenlees is a Toxicolo-

gist in the Toxicology Team in ONADE.

cine (CVM) Home Page on theInternet at: http://www.fda.gov/cvm/

guidance/published.htm#documents .Single copies of the guidance may beobtained by writing to the FDA Vet-

erinarian. Please send one self-ad-dressed adhesive label to assist inprocessing your request.

Written or electronic comments onthis draft guidance should be submit-ted by January 14, 2002, to ensuretheir adequate consideration inpreparation of the final document.General comments on Agency guid-ance documents are welcome at anytime. Submit written comments tothe Dockets Management Branch(HFA-305), Food and Drug Adminis-tration, 5630 Fishers Lane, Room1061, Rockville, MD 20852. Electronic

comments should be submitted to:http://www.accessdata.fda.gov/scripts/

oc/dockets/commentdocket.cfm.Comments should be identified withthe full title of the draft guidance andDocket number 01D-0501.

Additional information about thisdraft guidance document may be

found in the December 13, 2001, Fed- eral Register (http://www.fda.gov/

O H R M S / D O C K E T S / 9 8 f r /

121301b.htm), and from Dr. WilliamC. Keller, Center for Veterinary Medi-cine (HFV-210), Food and Drug Ad-ministration, 7500 Standish Place,Rockville, MD 20855, 301-827-6642, e-mail: [email protected] <mailto:

[email protected]>.

CVM SCIENTISTS ATTEND CONFERENCE ON TRANSGENIC ANIMALS(Continued)

DRAFT GUIDANCE ON PHARMACOVIGILANCE OF VETERINARYMEDICAL PRODUCTS AVAILABLE FOR COMMENT




Goal II of the Center for Veterinary

Medicine Strategic Plan states

that “We will improve and bring dis-

cipline to and through our business

practices by having . . . created a Cen-ter level project management func-

tion.” To implement this goal, CVMhas created a new Project Manage-ment Staff at the Center level, under

the direction of the Deputy Center

Director, Dr. Linda Tollefson. The newProject Management Staff will de-

velop and implement project man-

agement processes and methodolo-

gies to bring discipline to the way the

Center manages complex projects,

and provide the support and trainingnecessary to facilitate its effective

application across the Center.

As Director of the new Project Man-agement Staff, I will be holding meet-

ings throughout the Center over the

next few months to describe the func-

tions and terminology of project

management as a discipline, and to

share the Project Management StaffStrategic Plan. I look forward to get-

ting to know each staff member and

learning more about their views ofthe critical project management

needs of the various components of

CVM.The vision of the new staff is to

establish project management in

CVM as a culture and way of doing

business that adds value at all levels

of the organization. The Project Man-

agement Staff Strategic Plan outlinesthe goals and strategies for accom-

plishing this and its Implementation

Plan creates the roadmap for theirrealization. Included in that plan are

goals and strategies that will ulti-

mately reach out to all of CVM.

Almost anyone, when asked, can

give his or her own version of what

project management means to them.But for starters, a working definition

of team-based project management

can be stated as the process of plan-ning, focusing, coordinating, and

communicating the activities of a

project team to:

• Establish and manage a project

plan that is agreed to by all project

CVM ESTABLISHES NEW PROJECT MANAGEMENT STAFFby Madeline Van Hoose

team members and the organiza-

tions they represent

• Facil itate priority setting for

project objectives and tasks

• Facilitate the work of the project

team in accomplishing the project

goals and objectives

• Identify problems and issues earlyin the project

• Identify project resource require-

ments and conflicts early in theproject

• Facilitate decision-making and

problem-solving by the projectteam

• Improve coordination and com-

munication among the organiza-

tions represented by the projectteam members

• Improve communication with

principals outside the project

team

• Provide project status information

to senior managers for decision-

making

One of the goals of the ProjectManagement Staff is to create con-

sistency across CVM in the way we

approach and implement project

management. This will be a long-term effort that involves terminology,

methodology and process develop-

ment, standards and metrics devel-

opment, mentoring, training, and a

lot of piloting on real projects.

Our first pilot project for applica-

tion of team-based project manage-

ment is the development of the Anti-microbial Resistance Guidance For

Industry. I will be working with Dr. Bill

Flynn, the Team Leader, Mrs. Carole

Andres, the Project Manager, and allof the team members of the Antimi-

crobial Resistance Guidance Group

(ARGG) (Ms. Mary Bartholomew, Dr.

Kevin Greenlees, Ms. Aleta Sindelar,

Dr. Charlotte Spires, and Dr. DavidWhite), to apply the principles and

tools of project management to this

development effort. This project isvery complex and critically important

to the Center. It is an ideal example

where project management can help

achieve the goals of the project and

meet several critical and very tight

deadlines.

I see the initial benefits of a CVM

Project Management Staff as moreeffective project management for

larger, cross-functional CVM projects,a common project management vo-cabulary, a project management in-

formation system, well-defined and

repeatable project managementprocesses, and more readily avail-

able project management tools,

mentoring, and training. Over the

longer term, this will result in align-

ment of projects to the CVM Stra-

tegic Plan, a culture of collaborationand accountability, leveraging of

knowledge across the Center, and

increased internal and external stake-holder satisfaction. At a team level,

the benefits include expedited

achievement of project team goals

and deliverables, empowerment of

project team members through indi-

vidual accountability, and an en-hanced framework for critical deci-

sion-making.

The CVM Project ManagementStaff will be adding another staff

member to its ranks this year. In ad-

dition, short-term details will be es-tablished for project managers and

project coordinators to participate as

specific projects arise. Not only will

this help to incorporate project man-

agement tools and techniques into

organizations that allow thesedetailees to participate, but the

knowledge and skills they learn can

be applied to any project—large,small, complex, or simple. Mastering

these skills will open up new oppor-

tunities for individuals to apply them.

A CVM Project Management Team

will also be established as a less for-

mal structure to allow individualsfrom throughout CVM to participate

and learn about what project man-

agement is and how it can help intheir own organizations.

Madeline Van Hoose is Director of

CVM’s Project Management Staff.




12

FDA recently announced the first

metered-dose inhaler approvedfor use in horses. The active ingredi-ent, albuterol, is a new chemical en-tity never before approved for veteri-nary use.

Albuterol sulfate is administered tohorses intranasally via a metered-dose inhaler for the immediate reliefof bronchospasm and bronchocon-striction associated with reversibleairway obstruction [also known aschronic obstructive pulmonary dis-ease (COPD)] in horses.

Marketed under the trade name,Torpex, and sponsored by BoehringerIngelheim VetMedica, Inc., the drugis supplied in a pressurized alumi-num canister contained within anactuator system equipped with a de-tachable nasal delivery bulb. The na-sal bulb is inserted into the horse’snostril and when the horse inhales,the device is actuated providing apuff of aerosolized albuterol which isdelivered to the horse’s lungs.

The following firms/individuals re-ceived warning letters for offer-

ing animals for slaughter that con-tained illegal drug residues:

• Mike Bidart, Owner, Loyola Dairy,Chino, CA

• Charles F. Woodward, DVM,Concho Dairy Consulting,Onalaska, WI

• Shaye G. Pope, President, PopeDairy Enterprises, Stetsonville, WI

• Anthony R. Dinitto, Rome, NY• Randy J. Winner, Four Star Dairy,

Yorkshire, OH

These violations involved illegalresidues of penicillin in a dairy cow;extra-label treatment resulting influnixin meglumine residues in acow; illegal residues of gentamicin ina cow; illegal residues ofsulfadimethoxine in two cows; and,neomycin in a cow.

A warning letter was issued to the

following firms for violations relatedto 21 CFR Part 589.2000 – Animal Pro-teins Prohibited in Ruminant Feed.This regulation is intended to preventthe establishment and amplificationof Bovine Spongiform Encephalopa-thy (BSE) through feed.

• Kenneth Roy Tufly, Owner, DixonFeeds, Inc., Dixon, MT

• Gregory M. Sostak, President,Finlayson Ag Center, Finlayson,MN

Violations included failure to sepa-rate the receipt, processing, and stor-age of the product containing prohib-ited material from non-prohibitedmaterial; failure to establish a writ-ten system to avoid comminglingand cross-contamination of commonequipment; failure to maintainrecords sufficient to track the mate-rials throughout the receipt, process-ing, and distribution of products; and,failure to label products with the re-

quired cautionary statement “Do NotFeed to Cattle or Other Ruminants.”For example, the common scoopused to transfer prohibited materialfrom 50-pound bags to smallerbrown bags is not cleaned between

prohibited and non-prohibited mate-rial uses. Also, opened bags of pro-hibited materials were reported to bestored next to other open feed ingre-dient bags.

Ray Winn, President, Winn, Inc.,Smithfield, UT, received a warningletter for manufacturing a free choicefeed containing the Category II TypeA Medicated Article, Lasalocid/Bova-tec 68, for use in cattle and sheep.This firm failed to have an approvedformula, and failed to possess a valid

FDA Medicated Feed Mill License. Inaddition, the firm’s product labelscontained numerous errors.

Mr. LaMar G. Clements, President,Walton Feeds West, Inc., Cache Junc-tion, UT, received a warning letter for

selling and shipping a Type A Medi-cated Article (Lasalocid/Bovatec 68)to the above firm which does notpossess a valid FDA Medicated FeedMill License. As a manufacturer ofmaterials intended for animal feed

use, feed mills are responsible forassuring that the overall operationand the products manufactured anddistributed are in compliance with thelaw. This includes assuring that eachsite where the firm handles Type AMedicated Articles adheres to the re-quirement not to ship to unlicensedor unauthorized parties.

Mr. Louis A. Rodriguez, Vice Presi-dent, Pet Magic, Inc., Detroit, MI, re-ceived a warning letter for releasingpig ear dog treats that had been de-

tained by the Detroit District Officeinto commerce without the properrelease from the FDA. The samplestested positive for Salmonella .

REGULATORY ACTIVITIES

This aerosol dosage provides analternative to the approved drug,clenbuterol, an oral syrup. Aerosol al-buterol provides relief to affectedhorses within minutes allowing thehorse to breath easier. Typical adversereactions are transient sweating,muscle tremors, or excitement.

NEW DOSAGE FORM DRUG APPROVED FORHORSES

by Karen A. Kandra

P h o t o

b yN or m anW a t k i n s




On November 7, 2001, Investiga-tor Karen Robles from FDA’s

San Francisco District Office pre-sented the FDA’s Illegal Drug Resi-dues in Meat & Poultry Program atthe Pacific/Southwest Region MilkSeminar held in Reno, Nevada. Open-ing remarks were provided by Brenda

FDA INVESTIGATOR ATTENDS MILK SEMINAR

Holman, FDA’s Pacific Regional Direc-tor. There were representatives fromthe dairy regulatory programs in 22States, as well as 130 attendees at thetissue residue presentation, includingveterinarians, dairy producers, andState regulatory officials. Topics in-cluded program objectives, tissue

residue follow-up inspections, andthe most common causes of illegaldrug residues. Materials provided in-cluded FDA and the Veterinarian

booklets and press releases coveringrecent injunction cases.

Bimeda, Inc.(ANADA 200-144)

Oxytetracycline hydrochloride(Tetroxy)

Turkeys, swine. For the treatmentof various bacterial diseases.

ORAL—The ANADA provides for azero-day withdrawal time for use ofoxytetracycline hydrochloride in thedrinking water of turkeys and swine.Federal Register 11/26/01

SUPPLEMENTAL ABBREVIATED NEW ANIMAL DRUG APPROVALS

Company Generic and (Brand) Names Indications Routes/Remarks

First Priority, Inc.(ANADA 200-321)

Ivermectin(PrimectinTM Equine Oral Liq-uid) Rx

Horses. For treatment and controlof various species of internal andcutaneous parasites.

ORAL—The ANADA is a genericcopy of Merial Ltd’s Eqvalan® oralliquid for horses approved as NADA140-439.Federal Register 12/05/01

ABBREVIATED NEW ANIMAL DRUG APPROVALS



P h o t o b

yK ei t h W el l er

P h o t o b yK ar enK an d r a




14 ABBREVIATED NEW ANIMAL DRUG APPROVALS (Continued)


Vibrac AH, Inc.(ANADA 200-318)

Ivermectin(Virbamec Pour-On)

Cattle. For treatment and controlof various species of external andinternal parasites.

TOPICAL—The ANADA is a genericcopy of Merial Ltd’s Ivomec® Pour-On for Cattle approved as NADA 140-841.Federal Register 12/05/01


Schering-Plough AnimalHealth Corp.(NADA140-951)

Diclazuril(ClinacoxTM)

Turkeys. For prevention of coccidi-osis.

MEDICATED FEED—The supple-mental NADA provides for use of theapproved diclazuril Type A medi-cated article to make Type B andType C medicated turkey feeds usedfor prevention of coccidiosis causedby Eimeria adenoeides , E.gallopavonis , and E. melagrimitis .Also, the NADA establishes toler-ances for diclazuril residues in turkeyliver at 3 ppm, muscle at 0.5 ppm,and skin with adherent fat at 1 ppm.Federal Register 12/04/01

SUPPLEMENTAL NEW ANIMAL DRUG APPROVALS


P h o t o b y S c o t t B a u er





SUPPLEMENTAL NEW ANIMAL DRUG APPROVALS (Continued)

Pfizer, Inc.(NADA 141-053)

Carprofen(Rimadyl® Caplets) Rx

Dogs. For the relief of pain andinflammation associated withosteoarthritis.

ORAL—The supplement providesfor a once daily, 2 mg/lb dosage ofcarprofen, by oral caplet.Federal Register 12/05/01


MoorMan’s, Inc.(NADA 115-581)

Monensin(MoorMan’s Mintrate BlondeBlock RU and MoorMan’sMintrate Red Block RU)

Cattle. For prevention and controlof coccidiosis.

MEDICATED FEED—The supple-ment provides for use of approvedmonensin Type A medicatedarticles to make free-choice, medi-cated feed blocks used for preventionand control of coccidiosiscaused by Eimeria bovis andE.zuernii in pasture cattle.Federal Register 12/07/01





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US Food and Drug Administration: JanFeb