Center for Veterinary Medicine
FDA Home Page | CVM Home Page | CVM A-Z Index | Contact CVM | Site Map | FDA Centennial

horizonal rule
Spacer FDA Logo links to FDA home page HHS Logo links to Department of Health and Human Services website U.S. Food and Drug Administration Center for Veterinary Medicine

<<back

July/August 1997, Volume XII, No. IV, FDA Veterinarian Newsletter

FINAL RULE PROHIBITS MAMMALIAN PROTEIN IN SHEEP AND CATTLE FEED

FDA published a final regulation on June 5, 1997, that prohibits the use of mammalian protein, with certain exceptions, in the manufacture of animal feeds for ruminants. The rule will take effect August 4, 1997.

Recently, FDA published an Advance Notice of Proposed Rulemaking (May 14, 1996), a Proposed Rule (January 3, 1997), and a Draft Rule (April 17, 1997), all seeking comment on the best course of action to protect against the potential risk from BSE in this country. The Agency has received more than 1460 formal comments on this issue, and has held two open public meetings to discuss the most appropriate strategy.

The final rule establishes a flexible system of controls designed to ensure that ruminant feed does not contain animal protein derived from mammalian tissues, with certain exceptions, and to encourage innovation in such controls. FDA is taking this action because ruminants have been fed protein derived from animals in which transmissible spongiform encephalopathies (TSE's) have been found. Such proteins may cause TSE's in ruminants. TSE's are progressively degenerative central nervous system diseases of man and other animals which are fatal.

Epidemiologic evidence gathered in the United Kingdom suggests an association between an outbreak of a ruminant TSE, specifically bovine spongiform encephalopathy (BSE), and the feeding to cattle of protein derived from sheep infected with scrapie, another TSE. Also, there may be an epidemiologic association in England between BSE and a form of human TSE known as new variant Creutzfeldt-Jakob disease.

The final rule restricts the use of protein derived from mammalian tissues, with certain exceptions, in ruminant feed. Pure pork and pure equine protein are excluded because these animals are not known to have TSE's, and because the protein is processed so that it is not contaminated by potentially infective proteins.

FDA believes that it is prudent to take action prohibiting the use of certain animal protein products in ruminant feed even though BSE has not been diagnosed in the U.S., and there is scientific uncertainty as to its origin, transmissibility, etc. This final rule will prevent the establishment and amplification of BSE in the U.S. through feed, an action the Agency believes is necessary to protect animal and public health. Copies of the final rule are available for review or downloading on CVM's Internet Website and from the FDA Veterinarian.

FDA ORDER PROHIBITS EXTRALABEL USE OF FLUOROQUINOLONES AND GLYCOPEPTIDES

In the May 22, 1997 Federal Register, The Food and Drug Administration (FDA) issued an order prohibiting the extralabel use of fluoroquinolones and glycopeptides. The Agency issued this order because it believes that some extralabel uses of fluoroquinolones and glycopeptides in food-producing animals are capable of increasing the level of drug resistant zoonotic pathogens (pathogens that are infective to humans) in treated animals at the time of slaughter. In the order, FDA determined that some extralabel uses of fluoroquinolone and glycopeptide drugs in food-producing animals likely will cause an adverse event, which constitutes a finding under the Animal Medicinal Drug Use Clarification Act of 1994 (the AMDUCA) that extralabel use of these drugs in food animals presents a risk to the public health. Therefore, the Agency issued the order of prohibition.

On October 22, 1994, the President signed the AMDUCA into law. The AMDUCA amended the Federal Food, Drug, and Cosmetic Act to allow licensed veterinarians to prescribe extralabel uses of approved animal drugs and human drugs in animals. Section 2(a)(4)(D) of the AMDUCA provides that the Agency may prohibit an extralabel drug use in animals if, after affording an opportunity for public comment, the Agency finds that such use presents a risk to the public health.

FDA intends to prohibit by order the extralabel use of fluoroquinolones and glycopeptides in food-producing animals because the Agency has determined that use of these drugs other than for the approved label indications in food-producing animals meets the criteria for prohibition in the AMDUCA. Under this order, fluoroquinolones and glycopeptides were added to the list of those drugs already prohibited for extralabel use. The revised list states that the following drugs, families of drugs, and substances are prohibited for extralabel animal and human drug uses in food-producing animals.

 

  1. Chloramphenicol;
  2. Clenbuterol;
  3. Diethylstilbestrol (DES);
  4. Dimetridazole;
  5. Ipronidazole;
  6. Other nitroimidazoles;
  7. Furazolidone (except for approved topical use);
  8. Nitrofurazone (except for approved topical use);
  9. Sulfonamide drugs in lactating dairy cattle (except approved use of sulfadimethoxine, sulfabromomethazine, and sulfaethoxypyridazine);
  10. Fluoroquinolones; and
  11. Glycopeptides.

The order of prohibition is effective August 20, 1997. Written comments on this order are to be submitted by July 21, 1997, to the Dockets Management Branch (HFA-305), Food and Drug Administration, 12420 Parklawn Dr., Room 1-23, Rockville, MD 20857. Comments should contain the Docket Number, 97N-0172.

Information on this prohibition is contained in the Federal Register which is available for review or downloading on CVM's Internet Website. Paper copies are available from the FDA Veterinarian, telephone 301-594-1755.

Questions about this order may be directed to Richard L. Arkin, Center for Veterinary Medicine (HFV-238), Food and Drug Administration, 7500 Standish Place, Rockville, MD 20855, 301-594-1737.

NATIONAL FOOD SAFETY INITIATIVE ANNOUNCED

by Karen A. Kandra

On January 25, 1997, President Clinton announced a new initiative to improve the safety of the nation's food supply. The President announced he would request $43.2 million in his 1998 budget to fund a nationwide early-warning system for foodborne illness, enhance seafood safety inspections, and expand food safety research, risk assessment, training, and education. President Clinton also directed the Secretary of Agriculture, the Secretary of Health and Human Services, and the Administrator of the Environmental Protection Agency to work with consumers, producers, industry, States, universities, and the public sector to identify additional ways to reduce the incidence of foodborne illness and to ensure our food supply is the safest in the world.

Six agencies in the Federal government have primary responsibility for food safety: two agencies under the Department of Health and Human Services (HHS) -- the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC); three agencies under the Department of Agriculture (USDA) -- the Food Safety and Inspection Service (FSIS), the Agricultural Research Service (ARS), and the Cooperative State Research, Education, and Extension Service (CSREES); and the Environmental Protection Agency (EPA). Recently USDA, FDA, CDC, and EPA have worked together to build consensus and to identify opportunities to better utilize their collective resources and scientific expertise, and to strengthen partnerships with private organizations. As directed by the President, these agencies have now developed a strategy to improve systems of coordination, surveillance, inspections, research, risk assessment, and education.

It is estimated that foodborne illness causes as many as 9,000 deaths in the United States each year. Several population groups such as persons with lowered immunity due to HIV/AIDS and those on medications for cancer treatment or organ transplantation, as well as pregnant women, young children, and the elderly have increased susceptibility to foodborne infections. Patients taking antibiotics or antacids are also at greater risk of infections from some pathogens. The consequences of foodborne disease are particularly serious for those with inadequate access to health care, such as homeless people, migrant farm workers, and others of low socioeconomic status.

Sources of Foodborne Contamination

Bacteria and other infectious organisms are pervasive in the environment.

 

Foodborne infections can result in very serious immediate consequences, such as spontaneous abortion, as well as long-lasting conditions, such as reactive arthritis, Guillain-Barre syndrome (the most common cause of acute paralysis in adults and children), and hemolytic uremic syndrome (HUS), which can lead to kidney failure and death. Some of the microbial pathogens that have been the source of foodborne illness cases and outbreaks recently include, Salmonella, Campylobacter, Shiga-like toxin-producing Escherichia coli, Vibrio, Toxoplasma gondii, Cryptosporidium parvum, Norwalk virus, and hepatitis A. In addition, naturally occurring mycotoxins and marine toxins may contaminate foods and cause foodborne illness.

The Food Safety System

The current system for protecting food is a complex and diverse system based on regulatory authority divided among Federal, State, and local governments. The system cannot properly identify, track, and control food-related illness, or prevent future cases from occurring. In 1981, FDA inspected food firms every 2-3 years, but can now only visit those firms on average, once every 10 years (although some plants that produce higher-risk foods may be inspected more frequently). The Clinton Administration has taken the following steps to improve the safety of the food supply:

 

These advances are significant, but they are not enough. New pathogens, new food products, huge increases in imported foods, the growing importance of food exports, and increasing antimicrobial resistance among foodborne pathogens present new challenges to the nation's food safety programs.

Under this new initiative, the Federal government, in concert with State and local governments, industry and academia, would conduct research and risk assessments and cost-benefit analyses to determine how foodborne illnesses occur and can be controlled in the most efficient and cost-effective manner; improve surveillance and investigative efforts to locate and monitor illnesses caused by food; achieve more effective and efficient monitoring of the safety of the food supply through inspections of food processors; and reinvigorate education of all those involved in food preparation focusing on the use of safe practices.

PROTECTING PETS IN A DISASTER

by Karen A. Kandra

When we think of "disasters" we usually envision large scale emergencies, such as earthquakes, floods, tornadoes, etc. However, much more common are personal disasters which could be just as devastating to individual families as a huge cataclysmic event. House fires, extended power outages, car accidents, or sudden hospitalization are examples of events which may call for alternative care of our pets.

Preparation

It is best to prepare an emergency response plan prior to any crisis to avoid suffering to our four-legged friends. The American Red Cross provides excellent materials which will also help you and your family to develop an emergency plan. You should decide ahead of time who will be responsible for pet care if any emergency strikes. Choose the best room in the house to leave your pet if necessary. Make arrangements with neighbors. Be sure they have keys to your home along with specific information as to what pets are there, where they are located, and instructions for any medication needed. It also helps if your pets are familiar with your neighbors ahead of time, so they will not be dealing with strangers, and adding to the stress. Train your pet to a crate. In a crisis, he may need to be transported, and the ordeal will be less stressful if the crate is a comfortable and familiar place. Always keep pet's vaccinations current.

It is a good idea to prepare a disaster kit for your pet which should include: collars, tags, and leashes, a muzzle or gauze bandage, two-week supply of dry food, water, bowls, paper towels, and plastic bags for waste clean-up, and copies of pet's medical and vaccination records. Your pet's crate should be labeled with the pet's name, your name, and where you may be reached, or an out-of-area phone contact, if phone lines are down, and any specific medical instructions for the animal.

Prepare a telephone tree, with numbers of family, friends, veterinarian, local animal control, or shelter, local hotels which accept pets, etc.

During the Disaster

Animals can sense danger, and may panic and try to hide when fearful. To avoid injury and escape, crate the pet immediately, if a crisis is imminent. In certain emergencies it may be necessary to temporarily evacuate the area. This may include evacuation of animals. For pets, veterinary hospitals, boarding kennels or fairgrounds may be utilized as holding facilities, where it is not possible for animals to accompany their owners to emergency shelters. Under no circumstances should you ever leave your pet tied up or loose to fend for themselves. It is best to leave them in a room without windows, such as a bathroom, to prevent them from escaping or being injured from broken glass, in certain situations. If they will be left for several days, leave thick newspapers to absorb waste, and warm bedding. Remember, there may be extended power outages. Unplug all electrical applicances, and cover all electrical outlets with plastic or duct tape to avoid electrocution. If you have two of the same type of animals who get along well, leave them together for company. Keep exotic pets in separate rooms, since many reptiles can be dangerous to disaster personnel who do not know how to handle them. Post signs on door indicating what is in the room.

Be sure to provide a large supply of water in a heavy bowl which will not tip over, or leave water in tubs, or sinks, where the animal has access to it. Remove all flammable and poisonous chemicals from the room, and turn off all electricity.

After the Disaster

The behavior of pets often changes following a disaster. Normally quiet cats and dogs may become aggressive or defensive. Recovery from the disaster may take several days, weeks, or months. During the period of adjustment here are some recommendations:

  1. Check your pet for injury and/or exposure to chemicals. Consult your veterinarian when in doubt.

  2. Use care when releasing your pet from their crate. Familiar scents and sights may be gone. Downed power lines, or debris may pose serious threats to animals. Release only into an enclosed room or yard to prevent escape.

  3. If your pet was without food and water for an extended time, allow him to eat/drink small amounts every few hours.

  4. Allow your pet to have plenty of sleep and provide familiar toys while it becomes re-acclimated to its surroundings.

Hopefully, you will never face a major disaster, but it pays to remember your pets as part of your household disaster planning. If you must evacuate your home, it is best to take your pets with you. However, if you must leave them behind, advance plans for their care will ensure their health and safety.

The author acknowledges Dr. Sebastian E. Heath, B.SC., VetMB, MvetSci, MRCVS, Dipl.ACVIM, and Dr. Joseph Paige, D.V.M., M.P.H. for providing assistance in the preparation of this article.

WIDESPREAD EMERGENCE IN THE UNITED STATES OF MULTIPLE DRUG-RESISTANT TYPE OF SALMONELLA TYPHIMURIUM

by Marissa A. Miller, D.V.M., M.P.H.

As the Institute of Medicine stated in its Emerging Infections Report1, "in the context of infectious diseases, there is nowhere in the world from which we are remote and no one from whom we are disconnected." An infectious disease threat that has first been described in the United Kingdom is now being widely recognized in the United States. This threat is the emerging infectious agent,Salmonella serotype typhimurium known as Definitive Type 104 (DT104) . A multidrug-resistant strain, Salmonella typhimurium DT104, has increasingly been associated with difficult to treat Salmonella infections in man and animals and increased deaths due to Salmonellosis in the United Kingdom. This article will review what is known about Salmonellosis, describe characteristics of the pathogen, and provide an overview of DT104 in the United States.

To put this new threat to public health in context, some statistics relating to human salmonellosis should be reviewed. Salmonellosis is the most common bacterial foodborne disease, and third most common reported infectious disease in the U.S. 2. It is usually a mild, self limiting disease, but may result in serious illness. An estimated 2-4 million cases occur each year and result in an estimated 500 deaths. Whereas this infection is not usually treated with antibiotics, in the case of invasive disease which occurs in approximately 6 percent of the infections, treatment with antibiotics is required. S. typhimurium is the second most common serotype causing human disease, following closely behind Salmonella enteritidis which is most frequently associated with shell eggs.

The characteristic that makes the DT104 organism such a significant public health threat is its multidrug-resistant status. This microbe has a unique antibiogram--showing resistance to ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline. This penta-resistant pattern is referred to as R-type ACSSuT. The clone in the U.K. has additionally acquired resistance to fluoroquinolones and trimethoprim3. Whereas most resistance in Salmonella species is plasmid-mediated which means the removal of selective pressure (cessation of drug use) will over a period of time (usually years or longer) lead to reversion to susceptibility. In the case of penta-resistant DT104 the resistance genes are chromosomally integrated meaning removal of selective pressure is expected to have no effect on resistance.

In addition, the fluoroquinolone resistance that has emerged in DT104 isolates in the U.K. is also chromosomally integrated. This resistance is increasingly found in outbreak-associated DT104 isolates and highly correlated with severe disease and increased hospitalization stays. Ciprofloxacin (a fluoroquinolone) is currently the treatment of choice of invasive Salmonella infections in adult humans. The development of fluoroquinolone resistance in a strain of Salmonella that causes serious human illness could have significant public health and regulatory implications. It is unclear if DT104 is more invasive than other Salmonella strains, however, it has been shown to be more resistant to heat, desiccation, and chemical disinfection.

Largely as a result of the existence of Salmonella surveillance accomplished by the Centers for Disease Control and Prevention (CDC) and collaborative monitoring of antimicrobial resistance conducted by FDA/CVM, CDC, and USDA through the National Antimicrobial Susceptibility Monitoring Program (NASMP), public health agencies have a considerable information base about DT104 in the United States. DT104 has been identified from humans and a large diversity of animal species. The DT104 isolates from man and animals have been collected from widely distributed geographic areas. Several outbreaks of DT104-associated Salmonellosis have been described in man and animals. Foodborne transmission as well as direct animal-to-man transmission has been described.

The human data reported by CDC have shown an increase in 1990 from 7 percent of Salmonella typhimurium isolates showing the characteristic ACSSuT pattern of resistance present to 33 percent in 1996. When tested further, 11 out of 13 of the penta-resistant isolates turned out to be identical to the DT104 clone in the U.K. The 1996 data show the penta-resistant strains to be more invasive, 13 percent of R-type ACSSuT were from blood as compared with 4 percent of other Salmonella typhimurium isolates. CDC currently is conducting a FOODNET Case-Control study to further characterize DT104 infections. Preliminary data show increased hospitalization rate and duration associated with DT104 infections, animal contact as a possible risk factor, and both observations are consistent with reports of the U.K. experience. The case-control study is to be completed in August.

The NASMP's veterinary testing conducted by the Agricultural Research Service, USDA has also identified DT104 isolates from animals. In 1997, 8 out of 45 penta-resistant strains were DT104, all associated with one outbreak in swine in Nebraska. Testing conducted by the National Veterinary Services Laboratory, USDA has shown the proportion of Salmonella typhimurium isolates submitted from veterinary diagnostic laboratories going up slowly and in 1996 overtaking Salmonella enteritidis as the most common serotype. Of 549 Salmonella typhimurium isolates tested in FY1997 143 (26 percent) showed the ACSSuT pattern of resistance and 90 out of 143 (63 percent) were identified as DT104. The animal sources that DT104 had been collected from included: cattle, swine, chickens, turkeys, wild birds, rodents, exotics, and cats. These isolates were received from widely distributed geographic areas.

Apparent increases in the incidence of Salmonellosis in dairy herds and increased severity of disease have been reported in several areas and are stimulating research. Outbreaks of Salmonellosis due to DT104 have been reported in dairy herds in the Pacific NW and New York State and in feedlot cattle in the Pacific NW. These reports have been linked with human DT104 disease.

Several foodborne disease outbreaks resulting from DT104 have been reported. Last year in Nebraska an elementary school reported DT104-Salmonellosis believed to be associated with expired chocolate milk or exposure to sick animals. In California numerous cases of Salmonellosis were traced to DT104-contaminated Mexican-style soft cheese. An outbreak of DT104 is being investigated in Vermont in association with a dairy farm.

Much of the information presented in this article was brought forward at a May 1, 1997 "DT104 Workshop" hosted by CDC, National Center for Infectious Disease which took place in Atlanta, Georgia. Information was exchanged by participants from USDA, FDA, CDC, and academia. Participants representing the U.S., Canada, and the U.K. attended. The meeting also served to brainstorm research and public health strategies. Funding anticipated for FY1998 from the President's Food Safety Initiative will go towards improved surveillance of disease, resistance monitoring, and response activities relating to DT104 and other emerging foodborne pathogens.

1. IOM. Emerging Infections: Microbial Threats to Health in the United States. Institute of Medicine, Joshua Ledergerg and Robert E. Shope and Stanley C. Oaks, Jr. Editors. National Academy Press, Washington, D.C.

2. CDC. Salmonella Surveillance Annual Tabulations Summary 1993-1995. U.S. Department of Health and Human Services, November 1996.

3. Threlfall EJ, Frost JA, Ward LR, Rowe B. Increasing spectrum of resistance in multiresistant Salmonella typhimurium. Lancet 1996;347:1053-4.

4. Hosek G, Leschinsky D, Irons S, et al. Multidrug-Resistant Salmonella Serotype Typhimurium--United States, 1996. MMWR, April 11, 1997.

DRAFT HORSES -- PAST AND PRESENT

By Karen A. Kandra

When many people think of "Draft Horses", they probably picture a team of heavyweight horses plowing a field in the "pioneer days". It is true, these strong animals were used for farm work of all kinds before the days of modern tractors and other farm machinery.

All the draft horse breeds--Percherons, Belgians, Clydesdales, Suffolks, and Shires, originated in Europe, where draft horses served as car, truck, and tractor. Heavy loads had to be hauled up to 100 miles to the nearest railroad station. Even in the early days of America, young draft horses were put into service at 18 months, when they were hitched to the plow or wagon with older horses. Work horses were a necessity not only on the farm, but also in big cities around warehouses, freight terminals, and wharves.

With the onset of World War I, there came a demand for heavy horses which could pack supplies and ammunition, and haul artillery to the front. Following the War, the market for these heavy horses declined. An increased demand for American grain exports, and the introduction of gasoline powered tractors hastened the replacement of work horses by machines. Unfortunately, thousands of these animals were slaughtered, and some of the breeds nearly disappeared. Pure-bred draft stock declined sharply from 95,000 registrations in 1920, to under 2,000 in 1945. Clydesdales and Shires were affected earlier than other draft breeds, since both breeds had been used primarily in the city. The heavy feathering on the feet of the Shire and Clydesdale was considered a maintenance problem on the farm, diminishing their popularity. The only draft horse market remaining was centered on the farms of the Midwest. The American farmer looked for a smaller, more economical animal, and Belgian breeders responded with a more compact horse, making the Belgian the most numerous U.S. draft breed by 1940.

In the early 1950's the work horse started to vanish as they were replaced by tractors, trucks, and all sorts of mechanized farm equipment. However, the gentle giants remained as crowd pleasers in circuses and state fairs.

With the oil shortages of the 1970's, draft horses again found a limited place in American agriculture. The draft horse is still a practical alternative in small scale and specialty operations. In selective tree harvesting, horses are very useful in logging operations for removing downed trees. Ecologically, they do considerably less damage to forest floors, work quietly, and do not pollute the air.

Today, draft horses are enjoying a renewed popularity, and are real crowd pleasers at exhibitions throughout the country. Pulling contests, as well as halter, conformation, and hitch classes, are popular events at local county and state fairs throughout the Nation. Probably the most famous draft horses are the Budweiser Clydesdales, often seen on television ads and on display at the Busch Garden Theme Parks throughout the U.S. The Budweiser Eight-Horse Hitch is exhibited throughout the country.

With this revival of interest, registration figures have risen steadily for all draft breeds over the past two decades. Drafts have become a popular choice to cross with lighter breeds such as Thoroughbreds to produce sport horses for foxhunting, eventing, trail riding, and pleasure.

Draft horses may weigh 2,000 pounds or more, and measure up to 19 hands high at the withers. This is quite impressive, since an average horse weighs half that and stands 15 to 16 hands. Draft breeds are known for their friendly, good-natured dispositions, and make steady, willing workers. Whether in the show ring, or working the fields, draft horses win the hearts of people wherever they are seen.

For further information about draft horses, see "The Draft Page" on the Internet at http://www.hoof.com. There are links to the various breeds as well as a list of activities and news about draft horses.

MEDICALLY NECESSARY VETERINARY PRODUCTS

by Neal Bataller, ME, D.V.M

CVM acknowledges that the shortage of certain animal drugs could result in undue animal suffering and animal production hardships. To anticipate and address such a situation, CVM developed the Medically Necessary Veterinary Product (or MNVP) Shortage Management policy in June of 1994. This policy is not industry guidance but rather guidance for CVM staff. The purpose of the policy is to allow CVM to prevent or alleviate shortages of MNVPs.

A product is considered to be an MNVP if ...

 

DRUG RESIDUES IN FOOD-PRODUCING ANIMALS

by Joseph C. Paige, D.V.M., M.P.H., and Frances Pell, B.S.

Today's consumer has an interest in food safety and the prevention of unwanted drug residues in the food supply. In the United States, the protection of the public from illegal residues is a shared responsibility between the United States Department of Agriculture (USDA)/Food Safety and Inspection Service (FSIS) and the Food and Drug Administration (FDA).

The USDA's FSIS is responsible for ensuring the wholesomeness and safety of meat and meat products intended for human consumption by inspecting animals delivered to slaughter houses and processing establishments, and by sampling and analyzing edible tissues taken from livestock at the time of slaughter and after slaughter to ensure that meat does not contain unlawful levels of drug residues. FSIS' National Residue Program (NRP), operates a comprehensive testing program intended to ensure that the nation's meat and poultry supply is free of potentially harmful chemical residues. The information serves as a transition to a future science-based residue program in FSIS.

The FDA is responsible for protecting the health and safety of the American public by ensuring that edible products intended for human consumption (e.g., meat, milk and eggs), that are obtained from animals treated with new animal drugs, do not contain unsafe levels of drug residues. The FDA's Center for Veterinary Medicine (CVM) is a Public Health Organization that enables the marketing of effective animal drugs, food additives, feed ingredients, and animal devices that are safe to animals, humans, and the environment.

The FDA/CVM Tissue Residue Reduction Program has both a preventive (public health) and regulatory approach. The goal of the program is to ensure that consumer exposure to drug residues in edible tissues of food animals in minimized. One of the basic functions of public health is the collection and analysis of data. This approach is being utilized by FDA to understand the complexity and frequency of occurrence of residues and identify areas in which preventive strategies can be applied. To this aim, a database is used to collect, store, and recover information gathered during FDA and State on-site follow-up of reported violative tissue residues. The information contained within the database is essential in planning, implementation, and evaluation of policies necessary for residue prevention, and to establish priorities among these policies.

The regulatory function of the Tissue Residue Program is to enforce the Federal Food, Drug, and Cosmetic Act (FFDCA). The FFDCA and regulations published in the Code of Federal Regulations represent the primary levels of authority that support the regulatory process. Meat with residues above established tolerances and with illegal residues that result from misuse of a drug, e.g., failure to observe withdrawal periods, is adulterated under the FFDCA under Title 21, United States Code, Section 342 (a)(2)(D). FDA will consider regulatory action against individual farmers, animal producers, or the responsible individuals when it is determined that their animals contain illegal residues in edible tissues in excess of any established tolerance. The tolerance is the maximal level or concentration of a drug or chemical that is permitted in or on animal feed ingredients or animal tissues at the time of slaughter.

The data contained in this report are from FDA tissue residue investigations of violators identified via FSIS monitoring and surveillance programs where the farm of origin and animal identification were definitive. The purpose of this report is to review reports of violative residues detected in the major slaughter classes during 1993, 1994 and 1995 to determine the frequency of occurrence of violative residues by slaughter classes and pharmacological classes. This information is useful to determine whether patterns of violations can be related to specific slaughter classes and pharmacological drug classes and if so, implement preventive measures.

Materials and Methods

Data was collected from the Tissue Residue Information Management System (TRIMS), a database of information generated from FDA follow-up investigations, and from the Residue Violation Information System (RVIS). RVIS is a database of information collected by the FSIS and FDA that pertains to violative residues found in meat and poultry in the United States.

Data collected for each violation included descriptive information such as animal slaughter classes (beef cows, dairy cows, bob veal/fancy veal, swine and poultry), causes of residue violations and frequency of occurrence of residue violations via drug class. Only violative residues followed-up by FDA or State investigators during the years 1993, 1994 and 1995 were included in this study.

Results

In 1993, 4,283 violative residues were found in 3,809 animals (some animals/carcasses had more than one violative residue). During that year, violative residues occurred predominately in culled dairy cows, veal calves (neonatal), and market hogs (barrows and gilts). Similarly in 1994, there were 2,937 violative residues in 2,514 violative animals, and in 1995, 4,156 residues were found in 3,417 animals.

In 1993, culled dairy cows accounted for 30 percent of the violations, bob veal 40 percent, market hogs 6 percent, and sows 2 percent. In 1994 and 1995 the top three slaughter classes were dominant with an increase in the cow slaughter class. For the three years beginning 1993, 1994 and 1995, descriptive reviews were done on 1,207, 1,076 and 754 investigative reports respectively.

During 1993, the drugs most frequently identified as causing residues included the following: penicillin 856 (20 percent), streptomycin 414 (10 percent), oxytetracycline 409 (10 percent), sulfamethazine 394 (9 percent), tetracycline 166 (4 percent), gentamicin 150 (4 percent) and neomycin 143 (3 percent). CAST positive samples accounted for 35 percent of violative residues identified for follow-up.

Residues caused by penicillin have decreased from 20 percent to 13.6 percent from 1992 to 1995. While the amino glycoside gentamicin has decreased, from 4 percent to 2.9 percent, the frequency of occurrence for neomycin has increased two-fold from 3 percent to 6.4 percent. Also of significance is the decrease in streptomycin residues from 10 percent in 1993 to 2.4 percent in 1995.

In 1993, the two most common sources of purchase for the drugs were the feed/farm supply store and the veterinarian. They accounted for 31 percent and 26 percent of the drug purchases respectively. In 1994, they accounted for 31 percent and 20 percent respectively. In 1995, they accounted for 38 percent and 23 percent, with the mobile peddler involved in 22 percent of the investigations.

During the three years of the study, violative residues were found in each of the major bovine and swine slaughter classes. In 1993 they accounted for 90 percent of the violations. In 1994, violative residues from bovine slaughter classes of cattle and calves accounted for 87 percent of the violations, market hogs and sows accounted for another 10.7 percent for a total of 97.7 percent of the total violations. In 1995, bob veal, culled dairy cows and cows-beef accounted for 89 percent of the residue violations.

Most of the violative residues occurred in the Pacific Region for each of three years of the United States. These were cattle (culled dairy cows and bob veal).

Poultry, minor species and equine accounted for 2 percent or less of the violative residues.

In analyzing the data for the frequency of occurrence of residues by route of administration it was noted that for each of the three years reviewed, injectable drugs followed by the oral route (feed, water and bolus), and intramammary infusion accounted for the majority of the violations investigated. Unknown accounted for a higher percentage than one would anticipate with a complete follow-up record and animal identification.

Discussion

The Food Safety and Inspection Service (FSIS) of the U.S. Department of Agriculture is charged under the Federal Meat Inspection Act and the Poultry Products Inspection Act with ensuring that meat and poultry sold in interstate commerce in the U.S. is safe, wholesome, and free of adulterating residues.

Residue testing of food animals slaughtered in the United States is divided into two major groups: population sampling plans, which consist of monitoring, exploratory, and surveillance, and individual enforcement testing. The USDA/FSIS National Residue Program (NRP) is currently under restructuring as the agency prepares for the transition to a HACCP-based residue program. The NRP is comprised of monitoring, surveillance, and special projects.

Population Sampling Plan

Monitoring: Sampling of specified animal populations to provide profile information concerning the occurrence of residue violations on an annual, national basis. Compounds considered for testing have established residue limits and they are selected based on risk profiles and laboratory methodology that meet regulatory standards. Samples are a statistically based random selection of normal-appearing tissues from passed carcasses. The number of specimens chosen provide a 95 percent probability of detecting at least one violation when one percent of the animal population is violative.

The principle purpose of the USDA/FSIS Monitoring Plan is to gather information on the occurrence of residue violations in passed carcasses from normal appearing animals. In the future, it will serve as a transition to a HACCP-based residue program, which will become effective in large slaughter plants in 1998.

The information generated from the residue monitoring plans will be useful to the USDA in developing its public health programs, and in providing information to industry and consumers regarding potential problem areas. For FDA, this information is incorporated in a database and is used in the identification and follow-up of producers, etc., where violative residues are detected in animals sold for human consumption. FDA and cooperating State agencies conduct on-site visits to the farms to assess drug use, husbandry causes of residue violations, and conduct educational efforts on the part of State investigators. First-time violators receive an educational visit by the state as the initial attempt to correct a residue problem.

Surveillance: Designed to distinguish components of the livestock and poultry population in which residue problems exist, to measure the extent of the problem, and to evaluate the impact of actions initiated to reduce the problem. In surveillance, the carcass and organs may be retained pending test results

Special Projects: Designed to acquire information about the occurrence of specific residues in livestock and poultry, where lack of precise slaughter data makes it impossible to design a statistically-based sampling plan for the specific animal population.

Individual Enforcement Testing

Individual Enforcement Testing consists of analysis of specimens obtained from individual animals or lots based on signs or herd history. Testing is performed to detect individual animals with violative concentrations of residues. It is emphasized in problem populations and used as a tool to prevent residues from entering the food supply.

As a result of structured residue testing programs, FDA and State follow-up and training initiatives, and producer-initiated residue control programs, it appears we are experiencing in the United States a reduction in the number of animals carrying illegal drug residues. The efforts of the FDA, USDA, States, and producer organizations must continue toward the goal of further reducing or eliminating these violations.

As part of the regulatory and enforcement process FDA attempts to determine the cause and source responsible for each violative residue. The dairy farms and bovine slaughter class (culled, bob veal, cows) were responsible for >90 percent of the violations. This is to be expected as the cattle, cows, beef cows slaughter classes have been culled for some reason related to illness or conditions that reduce their productivity. High violation rates in bob veal calves are attributable to illegal drug use and the age of these animals does not allow for the proper withdrawal period for many of the chemical drugs used illegally or in an extra-label manner in this slaughter class.

In this study, as with previous findings, culled dairy cows and bob veal represent animal populations with the highest risk for harboring drug residues, when presented for slaughter, because the proper withdrawal period has not been observed. The drug(s) most frequently associated with these slaughter classes was the amino glycoside/neomycin.

Many drugs are intentionally or inadvertently given to these animals (via milk replacers, or feeding of contaminated milk).

Tolerance/Withdrawal Period

The human food safety of new animal drugs is evaluated by the Toxicology and Residue Chemistry Branches within the Center for Veterinary Medicine. Information generated from the toxicology review is used to establish the safe concentrations for total residues in the edible tissues of food-producing species. Information obtained from the residue chemistry review is used to establish the tolerance and set withdrawal times for the new animal drugs. These activities are essential to ensure that potentially harmful residues of the drug will not occur in food derived from treated animals.

The tolerance is our legal enforcement level; it is the codified value in the Code of Federal Regulations (specifically 21 CFR 556). It represents the maximal level of the active principle of a specific drug or a metabolite that can be permitted in the tissue of an animal.

The withdrawal time is the time before marketing for slaughter during which the drug is not used in the animal. This allows the animal to deplete the drug in its system to a below tolerance concentration.

As part of the FDA investigative and educational process it was determined that husbandry practices and marketing of bovine slaughter classes may attribute to the violations observed in various slaughter classes. There is infrequent change of ownership with culled cows as they are sent to slaughter facilities directly or through auction markets.

Since most of the violations were detected in the bovine slaughter class by means of surveillance tests, there is selection bias operating, because culled cows and calves were more likely to be tested than the other slaughter classes. Extra-label use was observed in many of these violative animals.

Culled cows and bob veal calves continue to have the highest residue rates of all slaughter classes. We encourage producer and industry groups to assist in the Government's residue reduction programs. A cooperative educational effort is necessary for residue prevention and to maintain consumer confidence in the safety of our food supply.

References

1. Gibbons, SN. Kaneene, JB. Lloyd, JW. "Patterns of Chemical Residues Detected in U.S. Beef Carcasses Between 1991 and 1993." JAVMA 1996: 209: 589-593.

2. National Residue Plan 1994. United States Department of Agriculture, Food Safety Inspection Service, Science and Technology.

3. Paige, JC. "Analysis of Illegal Residues in Meat and Poultry." FDA Vet. 1993: 8:5-6.

4. Webb. J., Paige, J. "Residues in Food Animals: Regulatory and Veterinary Responsibility." In Howard, JL (ed): Current Veterinary Therapy: Food Animal Practice. 3rd ed. Philadelphia. WB Saunders. 1991.

5. Van dresser, WR. Wilcke, JR. "Drug Residues in Food Animals." JAVMA. 1989: 194: 1700-1710

VMAC MEETS TO CONSIDER QUALITY STANDARDS

The Food and Drug Administration's Veterinary Medicine Advisory Committee (VMAC) met on May 13-14, 1997, in Gaithersburg, Maryland. Center representatives, regulated industry, and the American Veterinary Medical Association made several presentations to the Committee regarding the appropriate quality for veterinary drug products, and perceived problems with the current quality standards. The Center presentations and discussions included: the regulatory scheme by which applications are evaluated and approved in CVM; chemistry, manufacturing, and control (CMC) and current good manufacturing practice (CGMP) requirements; sterilization processes validation; an FDA veterinarian's perspective on quality of animal drug products; the FDA Field's perspective on CGMPs and quality; adverse drug reactions; medically necessary veterinary products; and, headquarters compliance activities with respect to the CGMPs. The VMAC was charged with evaluating this information in light of the following two questions: 1. How should the term "clinically ineffective" be defined for purposes of the Animal Medicinal Drug Use Clarification Act (AMDUCA)? 2. How should a veterinarian go about determining whether a drug is clinically ineffective for a labeled indication, i.e., what steps should he/she take in making that determination? The Committee will provide their comments on these issues at the Fall meeting scheduled for November 12-13, 1997.

CVM VETERINARIAN ADVISES CHILEAN GOVERNMENT

Officials from the Government of Chile's Agriculture and Livestock Service, Ministry of Agriculture invited CVM's Dr. Haydee Fernandez to visit Chile as a consultant in matters concerning the approval process of veterinary products in the United States.

Since 1994, the drug registration process in Chile has been the responsibility of the Ministry of Agriculture. The Office of Registration is now being organized and the entire registration process is being revised. The new Office of Registration is working to establish requirements for the registration of veterinary products that protect and improve animal health, and protect the Chilean population from food contaminated with drug residues.

One of the Ministry of Agriculture's high priorities is to regulate the use of veterinary products in food-producing animals since their exported food products must comply with U.S. and Europe's human food safety requirements. Chile is a major exporter of seafood products, thus, much discussion focused on CVM's role in aquaculture, and drug approval requirements for drugs used in seafood.

Dr. Fernandez presented a conference on the regulations, and procedures related to CVM's animal drug approval process. Government officials from the Ministry of Agriculture, the National Fishery Services, and staff professionals attended the conference held on March 20, 1997. In addition, Dr. Fernandez provided consultation on a variety of other topics such as the use of feed and food additives; the registration of generic drugs; requirements for safety and efficacy in the target animal; human food safety of drug residues; scientific basis for the withdrawal of imidazoles, nitrofurans, and gentian violet; the use of fluoroquinolones, etc.

The Chilean Government is very interested in establishing a continuous consulting agreement between the Agriculture and Livestock Service and CVM. This type of partnering would create a harmonization beneficial to both Governments, and would further ensure the human food safety of products exported to the United States.

Dr. Fernandez is very much at home in Chile since she is a native of Chile and received her veterinary degree from the University of Chile. In 1996 she represented CVM at a workshop there concerning antibiotic residues in milk. In CVM, Dr. Fernandez works on CVM's Toxicology Team in the Division of Human Food Safety.

EQUINE EXPERT VISITS CVM

Dr. Frederik J. Derksen, D.V.M., Ph.D., Professor and Chair of the Department of Large Animal Clinical Sciences, Michigan State University, College of Veterinary Medicine recently visited CVM to gain first-hand knowledge of the drug approval process. Dr. Derksen is a renowned equine respiratory physiologist, and a Diplomate of the American College of Veterinary Internal Medicine. He also has authored well over 100 publications on the subject of equine respiratory disease. Dr. Derksen attended many meetings on current CVM activities, such as fluoroquinolone antimicrobials, Salmonella, and BSE. He also toured CVM's new animal research center at MOD II in Laurel, Maryland. Dr. Derksen believes that many opportunities exist for collaboration with academia and CVM. In this environment of shrinking resources, future joint endeavors would utilize scientific expertise, equipment, and facilities to benefit all parties. Dr. Derksen intends to return to CVM this fall.

CVM was pleased to host Dr. Derksen, and we were fortunate that he took time to present a seminar on Chronic Obstructive Pulmonary Disease in Horses, Diagnosis and Treatment. The seminar focused on bronchodilator therapy and inhalant drug administration.

FDA ANNOUNCES A PILOT PROJECT FOR NCIE SUBMISSION

The Food and Drug Administration (FDA) is announcing the Notice of Claimed Investigational Exemption (NCIE) Electronic Submissions Pilot Project developed by the Center for Veterinary Medicine (CVM). This project is intended to increase the efficiency of the review process of the investigational new animal drug file (INAD), the new animal drug application (NADA), the investigational food additive petition (IFAP), and the food additive petition (FAP) by providing for the electronic submission of NCIEs, commonly known as drug shipment notices.

The purpose of the pilot project is to determine the practicality and feasibility of electronic submission and review as an alternative to the current paper-based processes. The pilot, anticipated to begin September 8, 1997, and run for six months (March 9, 1998), is limited in scope in order to apply metrics to a defined set of variables to be evaluated at the conclusion of the project.

A copy of the draft guidance document for this pilot project may be obtained from the CVM Home Page or by calling the FDA Veterinarian at 301-594-1755. Further information about the pilot project is available from Charles J. Andres, Ph.D., Center for Veterinary Medicine (HFV-128), Food and Drug Administration, 7500 Standish Place, Rockville, MD 20855 by telephone (301-594-2604) or e-mail (candres@bangate.fda.gov).

PUBLICATIONS

An updated guidance document titled "Good Target Animal Study Practices: Clinical Investigators and Monitors" is now available from CVM's Communications Staff by calling 301-594-1755. It is also available on CVM's Home Page.

The purpose of this guidance document is to make recommendations to investigators and monitors concerning the conduct of clinical studies evaluating the performance of investigational new animal drugs. This guidance supercedes the "Guideline for the Monitoring of Clinical Investigations, January 1988," and replaces CVM's previous guideline #39 dated October 1992.

REGULATORY ACTIVITIES

The following firms/individuals received warning letters for offering animals for slaughter that contained illegal drug residues:

These violations involved illegal residues of streptomycin in a bull calf, gentamicin in a bull calf, penicillin in a cow, sulfadimethoxine in a cow, gentamicin in a cow, tetracycline in a cow, sulfamethazine in a bull, oxytetracycline in a bob veal calf, sulfamethoxazole in a calf, sulfadimethoxine in a cull dairy cow, and penicillin in a cull dairy cow.

Warning letters were sent to Western Feed Mills, Inc., Cedar Vale, KS, and Kay Dee Feed Co., Inc., Sioux City, IA, for violations from GMPs.

NEW ANIMAL DRUG APPROVALS

Company Generic and (Brand) Names Indications Routes/Remarks
Schering Plough Animal Health Co. (NADA 141-081) Orbifloxacin (Orbax ®) Tablets Rx Dogs. For management of diseases associated with bacteria susceptible to orbifloxacin. ORAL: Provides for 2.5 to 7.5 milligrams per kilogram body weight. Federal Register 5/29/97.
Novartis Animal Health U.S., Inc. (NADA 141-084) Milbemycin oxime/Lufenuron (Sentinel) ®Tablets Dogs. For prevention of heartworm disease caused by D. immitis, for the prevention and control of flea populations, control of adult A. caninum (hookworm), and the removal and control of adult T. canis and T. leonina (roundworm), and T. vulpis (whipworm) infections. ORAL: Provides for tablets containing 2.3 milligrams (mg.) milbemycin oxime/46 mg. lufenuron, 5.75 mg./115 mg., 11.5 mg./230 mg., or 23 mg/460 mg. per tablet. Federal Register 5/27/97.

ABBREVIATED NEW ANIMAL DRUG APPROVALS

Company Generic and (Brand) Names Indications Routes/Remarks
Phoenix Scientific, Inc.
(ANADA 200-174)		 Gentamicin Sulfate Oral Solution Neonatal Pigs, 1 to 3 days of age. For control and treatment of colibacillosis. ORAL: ANADA 200-174 is a generic copy of Schering-Plough Animal Health's Garason®Pig Pump. NADA 130-464. Federal Register 5/29/97.
Agri-Laboratories, Ltd.
(ANADA 200-185)		 Gentamicin Sulfate Soluble Powder (Gen-Gard ®) Swine. For use in drinking water for control and treatment of colibacillosis in weanling swine and for swine dysentery. ORAL: ANADA 200-185 is a generic copy of Schering-Plough Animal Health's Garacin ®, NADA 133-836. Federal Register 5/29/97.
Ivy Laboratories, Inc.
(ANADA 200-224)		 Trenbolone Acetate Implants Growing-Finishing Feedlot Steers and Heifers. For improved feed efficiency in Growing-Finishing Feedlot Steers. For increased rate of weight gain and improved feed efficiency in Growing-Finishing Feedlot Heifers. IMPLANT OR INJECTABLE: ANADA 200-224 is a generic copy of Roussel UCLAF's NADA 138-612. Federal Register 5/29/97.
Halocarbon Laboratories, Division of Halocarbon Products
(ANADA 200-200)		 Halothane Dogs, cats, and other non-food animals. For induction and maintenance of general anesthesia. INHALATION: ANADA 200-200 is a generic copy of Fort Dodge Laboratories Inc.'s NADA 14-170 for Halothane. Federal Register 5/29/97.
Ivy Laboratories, Inc.
(ANADA 200-221)		 Trenbolone Acetate and Estradiol Implants Feedlot Steers. For increased rate of weight gain and improved feed efficiency. IMPLANT OR INJECTABLE: ANADA 200-221 is a generic copy of Roussel UCLAF's Revalor®S, NADA 140-897. Federal Register 5/27/97.
Pennfield Oil Co.
(ANADA 200-026)		 Oxytetracycline Hydrochloride Soluble Powder Cattle, Swine, Sheep, Chickens, and Turkeys. For control and treatment of bacterial infections caused by oxytetracycline susceptible organisms. ORAL: ANADA 200-026 is a generic copy of Pfizer's NADA 8-622, Terramycin-343 soluble powder. Federal Register 4/30/97.
Phoenix Scientific, Inc.
(ANADA 200-192)		 Sulfadimethoxine Oral Solution Broiler and Replacement Chickens, Meat-Producing Turkeys, Dairy Calves, Dairy Heifers, and Beef Cattle. In broiler and replacement chickens for treatment of coccidiosis, fowl cholera, and infectious coryza. In meat-producing turkeys for coccidiosis and fowl cholera. For dairy calves, dairy heifers, and beef cattle (in drinking water and as a drench) for shipping fever complex, bacterial pneumonia, calf diphtheria, and foot rot. ORAL: ANADA 200-192 is a generic copy of Pfizer's NADA 31-205, Albon®12.5 percent concentrated solution. Federal Register 4/30/97.
Phoenix Scientific, Inc.
(ANADA 200-178)		 Amikacin Sulfate Injection Dogs. For genitourinary tract infections (cystitis) caused by susceptible strains of E. coli and Proteus spp., and skin and soft tissue infections caused by susceptible strains of Pseudomonas spp. and E. coli. INJECTABLE: ANADA 200-178 is a generic copy of Fort Dodge Labs. Inc.'s NADA 127-892 for Amiglyde-V®Injection. Federal Register 4/30/97.
Phoenix Scientific, Inc.
(ANADA 200-181)		 Amikacin Sulfate Solution Horses. For treatment of uterine infections. INTRAUTERINE USE: ANADA 200-181 is a generic copy of Fort Dodge Labs. Inc.'s NADA 127-892 for Amiglyde-V®Injection. Federal Register 4/30/97.
Phoenix Scientific, Inc.
(ANADA 200-177)		 Sulfadimethoxine Injection Cattle. For treatment of bovine respiratory disease (shipping ever complex), bacterial pneumonia, calf diphtheria, and foot rot. INJECTABLE: ANADA 200-177 is a generic copy of Pfizer's NADA 41-245, Albon®Injection 40 percent. Federal Register 4/29/97.
Agri-Laboratories, Ltd.
(ANADA 200-061)		 Flunixin Meglumine Rx Horses. For alleviation of inflammation and pain associated with musculo-skeletal disorders and visceral pain associated with colic. INJECTABLE: ANADA 200-061 is a generic copy of Schering Plough's Banamine®Solution, NADA 101-479. Federal Register 4/28/97.
Med-Pharmex, Inc.
(ANADA 200-191)		 Gentamicin Sulfate Solution Turkey Hatching Eggs. For use as an aid in the reduction or elimination of certain organisms. DIPPING SOLUTION: ANADA 200-191 is a generic copy of Schering Plough's NADA 92-523 for Garasol®Solution. Federal Register 4/28/97.

SUPPLEMENTAL NEW ANIMAL DRUG APPROVALS

Company Generic and (Brand) Names Indications Routes/Remarks
Hoffmann-LaRoche, Inc.
(NADA 135-321)		 Salinomycin, Roxarsone, Bacitracin Methylene Disalicylate Broiler Chickens. For prevention of coccidiosis and for increased rate of weight gain. MEDICATED FEED: Provides for using approved single ingredient Type A medicated articles to make Type C medicated broiler feeds. Federal Register 5/29/97.
Hoffman-La Roche, Inc.
(NADA 96-298)		 Lasalocid Cattle: Increased rate of weight gain. MEDICATED FEED: Provides for the removal of the international feed number (IFN) for the condensed molasses fermentation soluble ingredient of the free-choice, lasalocid, liquid Type C feed. Federal Register 5/27/97.
Pfizer Inc.
(NADA 113-232)		 Oxytetracycline (Liquamycin ®LA-200 ®) Beef Cattle and Non-Lactating Dairy Cattle, and Calves including pre-ruminating (veal) calves. INJECTION. Provides for subcutaneous use of oxytetracycline injection in addition to intramuscular and intravenous use. Federal Register 5/21/97.
Pfizer, Inc.
(NADA 140-940)		 Semduramicin (Aviax ”) Chickens MEDICATED FEED. Provides for revising the assay limits for Type C medicated chicken feed containing Aviax ” from 85 to 110 percent of labeled claim to 80 to 110 percent. Federal Register 5/9/97.
Rhone-Poulenc, Inc.
(NADA 39-417)		 Decoquinate Cattle, Sheep and Goats. For prevention of coccidiosis. MEDICATED FEED: Provides for use of 6 percent decoquinate Type A article to make 0.06 to 0.6 percent decoquinate Type B feeds to make 0.0015 to 0.059 percent decoquinate Type C feeds. Federal Register 4/29/97.
Spacer
horizonal rule

CVM A-Z Index | Contact CVM | About CVM | Site Map
FDA Home Page | Search FDA Site | FDA A-Z Index | Contact FDA | Privacy | Accessibility | HHS Home Page