Game Birds Take Another Shot at the Drug Approval Game
by Meg Oeller, D.V.M. and Steven D. Vaughn, D.V.M.
The game bird industry in this country includes the raising of pheasants, quail, partridges, ducks, and wild turkeys. These birds are raised for sale to restaurants, direct to consumers, or for release into hunting areas. The North American Game Bird Association (NAGA) conservatively estimates that 5 to 10 million pheasants, 5 to 12 million Bobwhite quail, 15 to 25 million Coturnix (Japanese) quail, 2 to 4 million Chukar partridges, 100 to 300 thousand Hungarian partridges, 500 thousand to 1 million Mallard ducks, and 100 to 200 thousand wild turkeys are hatched and raised in the U.S. each year.
These birds face all of the challenges faced by other animals raised in groups. They are subject to infectious diseases, parasitism, and production pressures which often necessitate the use of animal drugs. As minor species, they also face the problem that few animal drugs have undergone testing and review to gain FDA approval for them. A minor species is any other than horses, cattle (except veal), swine, dogs, cats, chickens, and turkeys.
In most cases, it is not economically worthwhile for a pharmaceutical company to pursue a minor use approval. The income from the sale of an animal drug for minor species use is limited to such an extent that it rarely can offset the cost of development, production and marketing. In many respects, minor species/minor use drugs are similar to "orphan drugs" in human medicine. Unfortunately, at the present time, unlike orphan drugs for human use, there is no statute that provides economic incentives for pharmaceutical sponsors to pursue animal drug approvals for minor species. This is an area worthy of further exploration.
The limited number of drugs approved for use in minor species places producers such as the game bird growers in a predicament. The producers are prohibited by law from treating their own animals with drugs that are not specifically approved for such a use. Under a policy of regulatory discretion, veterinarians are permitted to use animal drugs in an extra-label manner, including for minor species. The FDA policy on the extra-label use of animal drugs in food-producing animals defines the limits of regulatory discretion to exclude the production of a medicated feed containing an animal drug that was not specifically approved for that use.
Recently, the passage of the Animal Medicinal Drug Use Clarification Act (AMDUCA) essentially legalized FDA's regulatory discretion policy. AMDUCA created a legal means for minor species producers to gain access to drugs for use in their animals through a veterinarian. However, the provisions of the act did not completely address the needs of the minor species producers. Despite the value of using the services of a veterinarian, the economic value of many minor species animals is such that the producers cannot always justify the extra expense to treat their animals. Further, the husbandry practices for many minor species, including game birds, makes medication in the feed the most practical way to achieve appropriate dosing. For example, catching birds for multiple injections or oral dosing of medication is labor intensive and dangerously stressful for the birds. Game birds raised in large outdoor pens will preferentially drink rain water over medicated water making this method of drug administration unreliable.
The North American Game Bird Association is taking the initiative on behalf of its members to address this dilemma. The game bird producers want to work within the law, and protect the safety of their customers who consume game birds. They also want drugs available for use in their animals to be safe and effective. They recognize that the best solution is to get drugs approved specifically for their birds. Toward this end, the organization has followed the model of the aquaculture industry and established a committee to identify and prioritize the drug needs of the industry. Their president met with CVM's Center Director, USDA representatives, and the National Research Support Project #7 (NRSP-7) minor species program liaison to develop a long-term plan.
The NAGA has identified 14 animal drugs, already approved in other species, that are needed for the production of game birds. These include coccidiostats, antimicrobials, anthelmintics, and growth promotants. First priority projects will be for therapeutic needs.
Table I
| Drug | Species | Indication |
| Zoalene | Pheasants | Coccidiosis |
| Lasalocid | Pheasants | Coccidiosis |
| Sulfadimethoxine/Ormetoprim | Pheasants/Partridges | Coccidiosis & Cholera |
| Nitarsone | Partridges | Blackhead |
| Nitromide/Sulfanitran/Roxarsone | Pheasants/Partridges | Feed efficiency |
| Oxytetracycline | Pheasants/Partridges/Quail | Respiratory disease, Cholera, egg production & fertility |
| Chlortetracycline | Pheasants/Partridges/Quail | Same as above plus treatment for Salmonella and E. coli |
| Erythromycin | Pheasants | Respiratory disease |
| Penicillin | Pheasants/Partridges | Respiratory disease |
| Decoquinate | Pheasants | Coccidiosis |
| Monensin | Pheasants/Partridges | Coccidiosis |
| Tylosin | Pheasants | Mycoplasma & Respiratory disease |
| BMD/Bacitracin Zinc | Pheasants/Partridges/Quail | Feed efficiency & enteritis |
NRSP-7 assists groups such as the NAGA by providing administrative assistance and funding for studies to support minor use approvals. These studies are reviewed by CVM and subsequently published in a Public Master File (PMF). The studies are intended to support the drug's efficacy, safety to the treated animal, safety in human food, and safety to the environment. This data may then be referenced by a pharmaceutical company to support expansion of their label to include the minor use indication. The pharmaceutical companies provide the necessary manufacturing information, and in many cases, other support to complete the New Animal Drug Application. The following drugs have already been approved for use in game birds.
Table II - Drugs Already Approved for Use in Game Birds
| Drug | Species | Indication |
| Penicillin G procaine | Pheasant | Production |
| Bacitracin zinc | Pheasant | Production |
| Bacitracin methylene disalicylate | Pheasant | Production |
| Thiabendazole | Pheasant | Gapeworm |
| Amprolium | Pheasant | Coccidiosis |
| Penicillin G procaine | Quail | Production |
| Bacitracin zinc | Quail | Ulcerative enteritis/ Production |
| Bacitracin methylene disalicylate | Quail | Ulcerative enteritis/ Production |
| Salinomycin sodium | Quail | Coccidiosis |
| Monensin sodium | Bobwhite Quail | Coccidiosis |
| Lasalocid sodium | Chukar Partridge | Coccidiosis |
| Chlortetracycline hydrochloride | Ducks | Fowl cholera |
| Chlortetracycline calcium | Ducks | Fowl cholera |
| Iodinated casein | Ducks | Production |
| Novobiocin | Ducks | Fowl cholera/ Infectious serositis |
NRSP-7 has been instrumental in the approvals of 2 of the 5 drugs approved for use in pheasants, 3 of the 5 drugs approved for use in quail, and for the only drug approved for use in partridges. There are also 4 drugs currently approved for use in ducks. One of the products on the NAGA's list is already an NRSP-7 project which is complete and ready for publication. Two others are already projects with studies in progress. The other proposals are being examined for feasibility and potential sponsor support.
FDA's Center for Veterinary Medicine will continue to meet with NAGA and NRSP-7 representatives to discuss the data requirements that would be necessary to develop the drugs on the prioritized list. Working together, product development plans are being constructed. CVM will also assist NAGA and NRSP-7 by advising and offering suggestions in the design of the necessary studies.
The cooperative efforts of NAGA, NRSP-7, the FDA Center for Veterinary Medicine, and pharmaceutical companies should lead to the eventual approval of the necessary drugs for use in game birds. Achievement of this common goal will answer the needs of the regulated industry while protecting the public welfare without placing an undue financial burden on the pharmaceutical companies. That is good news for everyone.
Minor species issues will be discussed in detail at the 8th Bi-annual NRSP-7 Workshop to be held September 12 and 13, 1996, at the Holiday Inn in Bethesda, MD. The workshop is open to the public and is enhanced by the diversity of attendees. Interested readers are invited to participate in the Workshop.
Readers who wish to obtain further information on game bird production may contact the North American Game Bird Association at the following address: Walter Walker, Secretary, P.O. Box 2105, Cayce-West Columbia, SC 29171, telephone (803) 796-8163.
Further information on the NRSP-7 minor species program may be obtained from
Meg Oeller, D.V.M., FDA Center for Veterinary Medicine, HFV-130, 7500 Standish Place, Rockville, MD 20855, (301) 594-1650.
FDA AND UNIVERSITY OF MARYLAND FORM JOINT INSTITUTE
by Karen A. Kandra
On April 15, 1996, FDA signed a Memorandum of Understanding (MOU) with the University of Maryland to create a unique partnership designed to increase the quality of research and public health policy, and to promote more efficient use of research resources. Named the "Joint Institute for Food Safety and Applied Nutrition" (JIFSAN), this partnership will be jointly administered, and function as a multi-disciplinary research program.
FDA Commissioner David A. Kessler, M.D. and University of Maryland President, Dr. William E. Kirwan signed the MOU in the presence of many dignitaries, including: HHS Secretary Donna E. Shalala, Congressman Steny H. Hoyer, Senator Paul S. Sarbanes, Senator Barbara A. Mikulski, and Governor Parris N. Glendening.
The FDA is the leading Federal regulatory agency responsible for promoting and protecting public health, continually striving to keep its scientists abreast of the latest scientific developments, and often relying on consultation with other academic organizations. The University of Maryland is the Washington area's most comprehensive research institution, serving as the primary center for graduate study and research, and providing undergraduate instruction across a broad spectrum of academic disciplines. The MOU allows the pooling of the two organization's internationally recognized scientific expertise, equipment, and facilities.
It is expected that the collaborative research conducted by the Center and the University's scientists in the Joint Institute will include studies on risk assessment, nutritional analyses, and other scientific investigations contributing to the four major elements of FDA's food program:
In addition, FDA and University scientists will participate in seminars, workshops, and other scientific forums to expand their expertise. Similarly, graduate and undergraduate students will have access to specialized training, internships and independent research.
FDA's participation in the Joint Institute is enhanced by the recent decision of the General Services Administration to build a new facility for both the Center for Food Safety and Applied Nutrition and the Center for Veterinary Medicine in the College Park area, where construction is expected to be completed by the year 2000.
This cooperative relationship will benefit both organizations substantially by the interchange of expertise, which will ultimately strengthen the scientific and professional base of both FDA and the University of Maryland. There will be opportunities to network with other nearby health agencies and share specialized equipment. CVM's new state-of-the-art large animal research facility in Beltsville is nearing completion, with occupancy expected in early FY 97. The USDA's Animal Research Center is also a short distance from College Park. In this environment of shrinking resources, this joint endeavor will promote growth which may otherwise be impossible. The Joint Institute plans future partnerships with industry as well as other State and Federal Government agencies.
GENTAMICIN INJECTION FINAL RULES PUBLISHED
In the May 15, 1996 Federal Register, FDA published a final rule to reflect that two new animal drug applications (NADA's) held by Schering-Plough Animal Health were being combined into one, one NADA was being withdrawn, a supplemental NADA was being approved, and a tolerance for residues of gentamicin in chickens was being added.
The firm requested that NADA 47-486 for Garasol ® Injection (5 mg. gentamicin per ml) for turkeys be included in NADA 101-862 Garasol ®. The NADAs are combined as NADA 101-862. NADA 47-486 is withdrawn.
Schering-Plough also filed a supplemental NADA (101-862) providing for the use of 50 and 100 mg/ml gentamicin sulfate injection for turkeys at the same dosage and for the same indications as currently approved. In addition, Title 21, Part 566.300 of the Code of Federal Regulations, is amended to provide for tolerances for gentamicin residues in chickens as well as turkeys.
NEW COMMITTEE MEMBERS FOR VMAC
by Karen A. Kandra
Three new members have been selected to join FDA's Veterinary Medicine Advisory Committee (VMAC). The new members are Steven A. Barker, Ph.D., Colonel Nancy K. Jaax, D.V.M., and Ling-Jung Koong, Ph.D. They replace retiring members Dr. Debra Aaron, Col. Anthony Johnson, and Dr. Gaylord Paulson.
Dr. Barker is a Full Professor in the Department of Physiology, Pharmacology and Toxicology of the Louisiana State University School of Veterinary Medicine. He also serves as the Director of The Analytical Systems Laboratory, a central analytical facility for the School, The Laboratory for Residue Studies, a drug metabolism research facility operated under GLP regulations and The Equine Medication Surveillance Laboratory, an analytical facility for the monitoring of drug use in equine athletes. Dr. Barker also serves as the State Chemist to the Louisiana State Racing Commission. Dr. Barker is an outstanding chemist whose research has included several studies involving the pharmacokinetics, metabolism and clearance of veterinary drugs in food animals. He has also been directly involved in the development of methodology for the subsequent detection and analysis of such compounds in milk and tissues, including extraction, analytical separation, immuno- and other receptor-based assay detection systems and drug quantification. Dr. Barker represents the chemistry specialty in VMAC.
Colonel Jaax received her D.V.M. degree from Kansas State University. With over 17 years of experience in veterinary pathology, Colonel Jaax is highly qualified to represent the pathology specialty for VMAC. She completed her residency training at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID), and has been board certified with the American College of Veterinary Pathology since 1983. She has been the consultant for veterinary pathology to the U.S. Army Surgeon General since 1991. Her major research area is the pathogenesis of Ebola virus infection in animal models.
Dr. Koong received both his M.S. and Ph.D. degrees from North Carolina State University. He currently serves as Associate Dean in the College of Agricultural Sciences at Oregon State University. Representing the biometrics specialty for VMAC, Dr. Koong is an outstanding mathematician with experience in application of statistical procedures for assessing research derived from animal production experiments. Past positions held by Dr. Koong include Associate Dean for Research and Associate Director, Agricultural Experiment Station at the University of Nevada; Research Leader of the Production Systems Research Unit at the Roman L. Hruska U.S. Meat Animal Research Center; and Associate Professor of the Departments of Animal Science and Range Science at the University of California-Davis.
Dr. Donald Lein remains the chairman of VMAC, and other members include Dr. Bernard Curran, Dr. George Cooper, Sue Hudson Duran, Dr. Diane Gerken, Dr. Stanley Kleven, Dr. Gary Koritz, and Dr. Alice Wolf. VMAC members normally serve four-year terms.
In the Federal Register of August 29, 1994, FDA issued a proposed rule declaring that specified offal from adult (more than 12 months of age) sheep and goats is not generally recognized as safe for use in ruminant feed and is an unapproved food additive when added to ruminant feed. FDA proposed this action because the specified offal may contain the agent that causes scrapie, a transmissible spongiform encephalopathy (TSE) of sheep and goats.
Since the proposal was issued, the Agency has been evaluating the comments submitted on the proposal, monitoring the scientific advances made in understanding the interrelationships among animal TSE's, and participating in a number of national and international task force/symposia to better understand the bovine spongiform encephalopathy (BSE) epidemic in the United Kingdom (U.K.) BSE has been diagnosed in over 160,000 head of cattle in the U.K. Epidemiological evidence gathered in the U.K. suggests a link between an outbreak of BSE and feeding animals protein derived from ruminants.
In recent months, ten cases of a variant form of Creutzfeldt- Jakob disease (v- CJD), a spongiform encephalopathy in humans with a new clinical and neuropathological profile, have been identified in the U.K. The appearance of 10 cases of v- CJD raises a possibility of a link to BSE. However, a link with BSE cannot be confirmed on the basis of this evidence alone.
No cases of BSE have been diagnosed in the U.S. Despite the fact that there is no problem with BSE in the U.S., the Agency believes it would be prudent to take action to ensure that BSE will not become a problem. In the May 14, 1996 Federal Register, FDA published an Advance Notice of Proposed Rulemaking (ANPRM) soliciting comments on the issue of using protein derived from ruminants (for example, cattle, sheep, and goats) in ruminant feed. FDA is interested in receiving information and comments to use in assessing whether these proteins are safe for use as a ruminant feed. Additional information about the notice can be obtained in the Federal Register or by contacting Dr. George Graber, Center for Veterinary Medicine, HFV- 220, Food and Drug Administration, 7500 Standish Place, Rockville, MD 20855.
In addition to the ANPRM, on May 9, 1996, FDA issued a letter to manufacturers of FDA-regulated products for animals signed by Dr. Michael A. Friedman, Deputy Commissioner for Operations to reiterate the Agency's concerns previously expressed regarding BSE. The letter strongly recommended that firms manufacturing FDA-regulated products take whatever steps are necessary to assure themselves and the public that they are not using ingredients from cattle born, raised, or slaughtered in countries where BSE exists. The list of countries where BSE is know to exist is maintained by the U.S. Department of Agriculture. As of May 1996, those countries are as follows:
In another effort to deal with the issue of BSE and other transmissible spongiform encephalopathies, USDA's Animal and Plant Health Inspection Service (APHIS) and FDA's CVM co-hosted a symposium titled "Tissue Distribution, Inactivation and Transmission of Transmissible Spongiform Encephalopathies of Animals". The forum, which was held on May 13-14, 1996, fostered a scientific discussion on TSE and approaches to controlling animal products and feed in order to manage any risk of TSE to animal health.
At the symposium, government, industry, and other scientific experts presented information on risk management applied to TSE; current science on the tissue distribution, inactivation, and transmission of TSE; current commercial processing of animal proteins in the U.S.; HACCP application to the rendering industry; and the feed industry's use of rendered ingredients. USDA and FDA also discussed major actions being taken by their agencies on BSE. Additional information on these actions will be included in future issues of the FDA Veterinarian.
FEED SUPPLEMENTS FOR HORSES: BUYER BEWARE
The following article was adapted from a speech presented by Sharon A. Benz, Ph.D., PAS to the Annual Meeting of the American Horse Council, June 3, 1996, Washington, DC. The article provides information on feed supplements for horses which may be helpful for owners in making their purchasing decisions. Veterinarians and equine nutritionists may wish to duplicate this article and provide copies to their interested clients. As always, material which appears in the FDA Veterinarian is free of copyright and may be reproduced without permission.
FDA's Center for Veterinary Medicine is responsible for the regulation of animal drugs, medicated feeds, animal food additives, and devices for use in animals. Feed ingredients, food additives, and drugs used in horse feeds and supplements are subject to the exact same laws as feed ingredients, food additives, and drugs for other domestic animal species. These products are also regulated in the exact same manner.
Everyone who owns a horse wants it to look and perform at its best, and part of this is good nutrition. Therefore, owners are often searching for new feed supplements that will improve the horse's health or provide a competitive edge in the show ring or on the race track. Unfortunately, the subjective nature of most of the evaluations of equine performance lends itself to the promotion and sale of many dubious products. These products may not pose an imminent health threat to a horse, that is, if a horse eats them it will not be acutely harmed. However, the effects of their long-term or high-level use may not be known or their usefulness may not be supported by valid scientific research.
Legal Background
While most of us call the grains, hays, etc. that horses consume "feed," the Federal Food, Drug, and Cosmetic Act (the Act), defines it as food. That is, food is an article used for food or drink for man or other animals. In a precedent-setting judicial decision, "food" was described as an article that provides taste, aroma, or nutritive value. Foods are considered generally recognized as safe or GRAS as sources of taste, nutrition, or aroma.
A food additive as defined by the Act is a substance which directly or indirectly becomes a component or otherwise affects the characteristics of a food. A substance is not a food additive if it is generally recognized as safe (GRAS) for its intended purpose by scientists qualified by training and experience to make such a determination. Some examples of food additives are anticaking agents, pelleting aids, and preservatives. Under the Act, a food additive is unsafe unless a regulation is promulgated providing for its safe use.
The definition of a drug is pretty straightforward. A drug is any substance, food or non-food, that is used to treat, cure, mitigate, or prevent a disease. A drug is also any non-food substance that is intended to affect the structure or function of the animal. Drugs must be shown to be safe and effective for their intended use. Any product administered by injection is also considered a drug.
Part of what distinguishes a food from a drug or a food additive is the intended use. For example, when vitamin E is used as a source of an essential dietary nutrient, it is considered a food. If it is used to treat or prevent azoturia or tying up syndrome, it is a drug. The legal distinction between a food and a drug is critical in terms of FDA's regulatory authority. A new drug or new animal drug must be subject to an approval process prior to marketing. Adequate data from controlled scientific studies to demonstrate the safety and efficacy of the drug for its intended use are required before a drug may be approved. Unapproved drugs on the market are deemed adulterated drugs and may be subject to regulatory action. In contrast, the law does not require a food to be subject to a premarket approval process unless it is considered to be a food additive.
Going back to the vitamin E example, if the label for a vitamin E supplement bears claims that consumption of the product will treat, prevent, or otherwise affect azoturia or tying up syndrome, such claims establish the intent to offer the vitamin E supplement as a drug. Furthermore, since vitamin E is not approved for this use, it is considered an unsafe new animal drug under the Act. This vitamin E supplement would be subject to regulation by FDA as a drug as well as a food. A company must remove the drug claims to restore its regulatory status as a food.
Lastly, there are various products being called "nutraceuticals." There are no laws or regulations that define what a nutraceutical is. The term was coined to describe the increasing number of products offered for the prevention or treatment of disease but marketed under the guise of food supplements. These may include products that contain levels of essential nutrients beyond what is recognized for normal nutrition or contain nutrients that are not recognized as essential for the intended species, such as omega-3 fatty acids. Presently, these substances are considered new animal drugs if the labeling bears claims to treat or prevent disease. The Dietary Supplement Health and Education Act that was recently passed by Congress limits FDA's authority regarding these types of substances for humans. However, CVM's assessment of the new law is that it was not intended and does not apply to animal feeds. This assessment was published in the Federal Register on April 22, 1996.
Specific Examples
The following are specific examples of unapproved products and a discussion of why horse owners should think twice before buying them. The first group of supplements is products which fill no recognized nutritional need in the horse's diet. There are no acceptable research studies in peer-reviewed journals, nor has the Agency seen information to support the safety and usefulness of these products. Most of these products have only anecdotal information and some case studies attributed to them.
An example of this type of product is Gamma Oryzanol, which appears to be a relatively new product in the horse industry that is being publicized as a growth promotant and as a safe natural alternative to anabolic steroids. Gamma Oryzanol is an extract of rice bran and has not been proven safe or effective for use as a growth promotant in horses. There is one growth promotant approved for use in horses. That approval is for chlortetracycline for use as a growth promotant in horses under one year of age.
Octacosanol is a substance that is being promoted to improve endurance and speed reaction time, to strengthen muscles and to reduce oxygen debt. This substance is found naturally in small amounts as a component of plant waxes and some vegetable oils, notably wheat germ oil. It has not been shown to be safe and effective for any use in horse feeds.
Superoxide dismutase (SOD) or Dismutase is an enzyme that has a number of important oxidative functions in cells including red and white blood cells and muscle cells. It is often sold as a feed supplement for treatment of musclo-skeletal inflammation and stress, and for disease prevention. Since enzymes are proteins and proteins are digested in the gut, SOD would also be digested in the same way as other proteins in the diet are digested to amino acids or peptides for absorption. Therefore, it is unlikely that any intact enzyme would be absorbed and available to the cells in a horse's body. This product is basically a very expensive protein source.
Mucopolysaccharides are being promoted for use in feeds to increase synovial fluid viscosity in the joints and improve and strengthen the integrity of the joints. Mucopolysaccharides are components of connective tissue and joints. There are various forms of mucopolysaccharides on the market, such as glycosaminoglycans and chrondroitin sulfates. The products are most often derived from bovine trachea, animal cartilage, and Australian perna canaliculus mussel. When these products are promoted to treat non-infectious degenerative joint dysfunction of carpal joints in horses or to increase synovial fluid viscosity in the joints, they are considered unapproved new animal drugs because they have not been proven to be safe and effective for these purposes. When given orally, there is a question as to the extent of absorption of these compounds and how they reach the affected joint in sufficient amounts to have any effect.
Other products that are being promoted as digestive aids and sources of minerals are just normal components of soil such as humic acids and montmorilonite. Humic acids are the decomposition products of organic matter, particularly dead plants, and are found in the soil. Montmorilonite is a type of clay found in the soil which is permitted for use in the feed industry as an anticaking agent in feeds. These compounds are not approved and not shown to be safe as digestive aids and have not been proven to serve as a source of minerals to animals.
Diatomaceous earth, another substance taken from the soil, is being promoted as a natural dewormer. It is the silicon skeletons of ancient plankton that settled to the sea floor. It is an approved food additive as an anticaking agent or as an inert carrier not to exceed 2 percent of the diet. As a dewormer, it would be considered an unapproved new animal drug, and has not been shown to be either safe or effective for this purpose. In fact, there was a recent study that found diatomaceous earth was ineffective as a dewormer. This study, completed at the Virginia-Maryland Regional College of Veterinary Medicine, concluded that diatomaceous earth had no effect whatsoever on fecal egg counts or packed cell volume in sheep.
There is a product being promoted as vitamin B-15. It is also called Pangamic Acid and sometimes Dimethylglycine (DMG). Pangamic acid is a poorly defined chemical mixture allegedly isolated from apricot pits. These products may vary considerably in the composition. Some are mixtures of calcium gluconate and DMG and others contain diisopropylamine dichloroacetate, which is a drug. Pangamic acid is neither a vitamin nor a dietary requirement for any animal. Proponents claim that it decreases lactate production and plasma lactate levels after exercise and that it improves speed. Neither pangamic acid or DMG or diisopropylamine dichloroacetate has been proven safe or effective for any use in horse diets.
Another group of products includes nutrients that are being promoted for therapeutic effects. Tryptophan and magnesium are two nutrients--tryptophan is an amino acid and magnesium an essential mineral--that are being marketed for sedative and calming purposes. The amounts being used greatly exceed that needed for nutritional purposes. Tryptophan has been the subject of much scrutiny since several people who took tryptophan supplements developed Eosinophilic Myalgia Syndrome, which is a painful and crippling nerve degeneration disorder. Tryptophan is generally recognized as safe (GRAS) to improve the quality of the protein source at nutritional levels. Tryptophan has not been shown to be safe and effective for use as a sedative. Moreover, giving tryptophan in large doses for sedative purposes can cause severe amino acid imbalances and deficiencies in other amino acids, and can also be toxic. Similarly, large doses of magnesium can interfere with the utilization of other minerals and result in mineral imbalances.
Phenylalanine is another amino acid that is often promoted for therapeutic purposes as a painkiller. Phenylalanine is also GRAS when added in small quantities to diets to improve protein quality. It is not approved and has not been shown to be safe and effective as a painkiller. Like tryptophan, large doses of phenylalanine can cause severe amino acid imbalances and may be toxic.
Vitamins are an interesting subject because not all vitamins that are dietary essentials for one species are dietary essentials for other species. Vitamin C, or ascorbic acid, is a good example. Humans, non-human primates, guinea pigs, and rainbow trout have a dietary requirement for vitamin C because it can not be synthesized by the body. It is not a dietary essential for horses. Horses can synthesize vitamin C in their bodies. Moreover, the National Research Council's (NRC's) Nutrient Requirements of Horses states that horses do not absorb dietary vitamin C to any great extent. Some recent studies have indicated that older, geriatric horses may not be able to synthesize enough vitamin C to meet their requirements, but this has not been suggested for any other class of horse. Vitamin C, as well as various bioflavonoids, are often promoted to stop bleeding in racehorses. It has not been proven effective to stop bleeding and would be considered an unapproved drug for this purpose.
Another vitamin often promoted for use in horse diets is biotin, a B vitamin, which is a dietary essential for humans, pigs, chickens, dogs, and cats, among others. The horse's requirements for biotin, as for most of the B vitamins, should be met by bacterial synthesis in the cecum and large intestine with sufficient amounts absorbed to supply the animal's requirements without the need for dietary supplementation. The NRC's 1989 publication "The Nutrient Requirements of Horses" does not list a dietary requirement for biotin. No controlled studies have been published that establish a dietary biotin requirement above that supplied by intestinal synthesis. Some have theorized that biotin will promote hoof growth based on the fact that, in animals that have been shown to have dietary biotin requirements, a biotin deficiency is characterized by poor hoof growth. However, FDA is not aware of any data in peer-reviewed scientific journals that indicates that biotin has an effect on hoof growth in horses. Biotin products that make claims for increased or improved hoof growth are unapproved food additives.
Herbs and plant extracts are also marketed as feed supplements. Many herb products are marketed as sedatives. While many herbs are GRAS as spices, natural seasonings, or flavorings and are probably not unsafe to feed to horses, products often contain herbs that are not considered GRAS. There are no scientific data in horses on the safety and usefulness of herb products. Most information available on these products is anecdotal. Generally, the levels of the natural constituents in herbs can vary greatly as a result of the parts of the plant harvested, the growth stage of the plant at harvest, and processing methods. Herbs also contain chemicals that can be harmful, such as certain alkaloids. Toxicities have been associated with comfrey and chaparral in humans, and horsetail and snakeroot are known to be toxic to horses.
Advice for Horse Owners
While many of the products mentioned above are unlikely to do anything to benefit horses, they may be found in local feed or tack shops. These products are not removed from the market because most of FDA's limited resources must be focused on products or incidences that pose a known hazard to human or animal health. Thus, FDA does not always have the time or resources to take enforcement action against products that are more fraudulent than dangerous. This is also true of feed programs administered by State governments. Therefore, horse owners must protect themselves from fraudulent products. Horse owners should be aware of the following signs when considering purchasing feed supplements.
First, they should look for disclaimers on the label or promotional material that read: "This is not a drug," and then other statements on the label claim that the product prevents, mitigates, treats, or cures a disease. The FDA does not allow the use of disclaimers on approved products. So, if the product has such a disclaimer, it is not approved. These types of products may be indirectly unsafe to horses, if owners are trying to treat their own horses rather than seeking advice from their veterinarian.
Second, owners should look for exaggerated claims for a product or products that are too good to be true. These are products that may solve a variety of problems, make horses win at shows, improve mental attitude, etc.
Third, horse owners should look for statements on products that use scare tactics. For example, products that claim that a horse has been suffering from a deficiency for years and owners never knew it. Other products may claim that they are totally unique and unlike any other feed supplement on the market and that it contains vitamin X or a new special ingredient.
Lastly, horse owners should look carefully at the label and learn how to interpret them. All labels for feed supplements should have a statement that describes the intended use of the product, for example, a vitamin and mineral supplement. The label should also have a list of ingredients. Federal regulation requires that the ingredients be listed by the common or usual name in descending order of predominance by weight. The list of ingredients can also help owners distinguish between a poor quality supplement and a good quality one. For example, the relative availability of copper from copper oxide is very low and generally less than 10 percent when compared to the copper sulfate, which is highly available. Therefore, a poor quality supplement may list copper oxide as a source of copper.
Also, horse owners should look at the guaranteed analysis. For complete feeds, many States now require guarantees be given for crude protein, fiber, and fat; calcium; phosphorus; copper; selenium; zinc; and vitamin A. Guarantees should also be given for any other major nutrients in the feed or supplement that is emphasized in the labeling. For example, if a label states "Horse supplement X with Vitamin E," the vitamin E content of that supplement should be guaranteed on the labeling. In addition, quantities must be given in English units and there must be adequate directions for use on the label that can be practically followed. If the guarantees are not provided on a per serving basis, some simple calculations can provide owners with the amount per serving. Owners could then compare this figure to the daily requirement for that nutrient for the horse. Many times what looks like a great supplement may only provide 1 to 2 percent of the daily amount of a nutrient required by a horse!
An educated horse owner is the best horse owner. If horse owners have any questions about the safety or usefulness of a product, they should not hesitate to contact an equine nutritionist or their veterinarian. If horse owners still have questions, they may write to the Center for Veterinary Medicine.
RECENT CHANGES AND ADDITIONS TO THE CVM HOME PAGE
by Deborah Brooks
The FDA's Center for Veterinary Medicine (CVM) is committed to the continued development of its Home Page on the World Wide Web (WWW). This allows the public to have computer access to publications and current information from the Center. The CVM Home Page contains documents and information of interest to animal drug developers and manufacturers, veterinarians, and to a lesser extent, consumers, and pet owners. The material tends to be fairly scientific or regulatory in nature. The CVM Home Page address is:
http://www.cvm.fda.gov/
The site has recently been reorganized and updated to provide a variety of information. An Organizational Chart has been provided to assist the public in locating specific information. Public documents have been centralized in the INFORMATION RESOURCES LIBRARY. The Library contents are summarized below:
Other recent additions include revised phone listings for all of CVM, organizational charts, and the FDA Veterinarian. The FDA APPROVED ANIMAL DRUG PRODUCTS SEARCHABLE DATABASE is also still available.
Please note, that while many document types are available, all of the documents within that type may not be electronically accessible. For example, there are thousands of Freedom of Information (FOI) Summaries, however, only a small portion are available through the Home Page. Current FOI Summaries are added as they are produced, while older Summaries are added in blocks of 20-30 each month. In order to see recent additions to the Home Page, click on the "What's New on this Site" link. If a particular document is not on the Home Page, a hard copy may be requested from the Communications and Education Branch, HFV-12, 7500 Standish Place, Rockville, MD 20855.
The World Wide Web site is maintained for the Center for Veterinary Medicine by the Drug Information Laboratory at the Virginia-Maryland Regional College of Veterinary Medicine at the Virginia Polytechnic Institute, Blacksburg, VA. Questions and/or comments on the CVM Home Page may be made through the Comments link, or to Ms. Deborah Brooks, CVM's Home Page Manager. Ms. Brooks may be reached on 301-827-0215 or by e-mail at Deborah Brooks@BANGATE.FDAGOV. PLEASE NOTE: Comments made to the Comments link should only address the document or information content of the Home Page. It should NOT be used to request documents, query the status of an application, forward questions to CVM Staff, or ask about a drug prescribed by a veterinarian.
Health fraud flourishes in the animal drug and feed industries. Disease conditions in prized animals, such as racehorses or family pets, sometimes prompt animal owners to seek miracle cures and quick fixes. Additionally, products which promise greater profits to farmers and ranchers and products which promise certain conveniences or other advantages to animal owners may make for easy victims of health fraud.
Perpetrators of animal health fraud are easily able to target promotional campaigns to desired audiences. There are numerous trade press publications directed to consumers who are involved in various animal-oriented professions or avocations. There are dog fancier and hunting dog magazines, journals for pleasure horse or racehorse enthusiasts, and publications directed to all aspects of food animal production. Such publications allow for selected placement of advertisements, as well as provide mailing lists for health fraud promoters.
Not all false or misleading or inadequately substantiated claims made in conjunction with animal products are considered health fraud. The designation is normally associated with ineffective or unproven products for which a broad range of generalized medical/therapeutic or function claims or greatly exaggerated claims are made. For example, marketing an iron preparation intended for the prevention of anemia in baby pigs, in the absence of an approved NADA, would constitute a violation of the Act. However, it would not be considered health fraud since iron is essential to the prevention of anemia. On the other hand, marketing an electric shock device with claims to mitigate the effects of snake bite in cattle would be considered health fraud because the claim is false and without rational basis.
Health fraud products which present a direct health hazard to animals (or to humans) have the highest priority for enforcement. An example would be an electric dog training collar, which is shown to cause injury to dogs.
Economic fraud is of somewhat lower priority for enforcement in animal drugs and feeds. Examples include:
CVM attempts to make information regarding significant trends in health fraud available to the public through issuances of press releases, talk papers, and the FDA Veterinarian, and through the FDA Public Affairs and Health Fraud Staff and other communications channels.
Veterinary products suspected of being fraudulent or otherwise misbranded or adulterated should be reported to the FDA District Office.
CVM Health Fraud Contacts
Consumer Inquiries:
Linda A. Grassie, Public Affairs Liaison, (301) 594-5909
CVM Health Fraud Coordinator and Enforcement Inquiries:
Darrell E. Baker, (301) 594-1785
Veterinary Drug Inquiries:
Vitolis E. Vengris, D.V.M., (301) 594-1758
Veterinary Nutritional Supplements:
David A. Dzanis, D.V.M., (301) 594-1728
Medicated Feeds:
Malcolm C. Thomas, Ph.D., (301) 827-0172
CVM OFFICE OF NEW ANIMAL DRUG EVALUATION EXTERN PROGRAM
by Elizabeth Reese, D.V.M. & Thomas Letonja, D.V.M., M.S., Ph.D.
CVM has initiated a new program to foster continuing education of review scientists in the development, production, and evaluation of animal drugs by facilitating communication among regulatory and drug sponsor scientists. This new initiative, titled, the "CVM Extern Program," involves direct interaction between CVM and drug sponsor scientists. Time is split between the sponsor's headquarters and visits to external Study Investigators at study sites.
Broad areas of interest to CVM include animal drug feasibility studies, new animal drug discovery, animal drug development, efficacy evaluation, safety evaluation, and animal drug manufacturing.
The first Extern Program was successfully completed in Animal Health Product Development with Pfizer Central Research in Groton, CT. Drs. M. E. Reese (Division of Therapeutic Drugs for Non-Food Animals, Equine and Antimicrobial Drugs Branch, HFV-114) and Thomas Letonja (Division of Therapeutic Drugs for Food Animals, Antiparasitic and Physiologic Drugs Branch, HFV-135) participated in a two-week program (April 8 - 19, 1996).
The first week, Drs. Reese and Letonja visited Pfizer's research headquarters in Groton, CT. During this time, Drs. Reese and Letonja participated in an orientation tour of the facilities and an introduction of the animal health development organization and personnel. They also participated in ongoing Project Team activities and attended several meetings and discussions. Drs. Reese and Letonja presented a seminar to explain CVM's organization, the review process of a typical submission and our interactions with other Federal and State regulatory organizations. The seminar was well attended by Animal Health Product Development personnel and generated an animated exchange between CVM representatives and Pfizer's personnel.
The second week of the Program focused on the monitor visits of clinical trial sites. Time was arranged by each Project Team based on ongoing activities. The externs traveled to clinical investigator sites accompanied by Pfizer's monitors. Dr. Reese visited sites located in Louisiana and Texas, and Dr. Letonja interacted with external collaborators in Texas and Wisconsin. Back in Groton, the final day of the second week was reserved for discussion of the visit, the mutual benefits derived, and the future direction of the extern program.
Both the Pfizer participants and the CVM Externs were enlightened by all the issues discussed and enjoyed the free exchange of information between the two organizations.
by Sharon R. Thompson, D.V.M.
The Codex Alimentarius Commission was named as the international reference organization for health and safety measures relating to food in the Uruguay Round Text on Sanitary and Phytosanitary (SPS) Measures. This text was brought into force with the establishment of the World Trade Organization (WTO) on January 1, 1995. The WTO is the multilateral organization that will implement international trade rules and is the successor organization to the General Agreement on Tariffs and Trade (GATT).
The primary objective of the WTO is to liberalize world trade and place it on a secure basis, thus contributing to economic growth and development. The WTO also functions as the principal international body concerned with multilaterally negotiating the reduction of trade barriers and other measures that distort competition. Additionally, it serves as a place for countries to raise their concerns regarding the trade policies of their trading partners.
Prior to the WTO agreement, there were no effective international rules to distinguish trade-protectionist measures from legitimate import regulations to ensure food safety or to otherwise protect the health of people, animals, and plants. Under the SPS text, each nation can continue to make a sovereign determination of its acceptable level of risk. Alternatively, countries may use international standards. A nation utilizing an international standard such as a Codex maximum residue limit for veterinary drug residues is seen as meeting its obligations under the provisions of the SPS agreement.
The SPS agreement does recognize the right of countries to maintain standards which are stricter than international standards. However, stricter measures must be based on science and be justifiable as a consequence of a non-discriminatory lower level of acceptable risk. The SPS agreement is designed to curtail current import restrictions that are based on arbitrary and unsubstantiated health and safety concerns. It is also intended to prevent countries from avoiding commitments under the WTO agreement to open their markets.
Because of the awareness within Codex that issues related to veterinary drug residues were creating restrictions to trade in meat and meat products, a separate Codex Committee was formed in 1986 to develop standards to address this problem. The Codex Committee on Residues of Veterinary Drugs in Food (CCRVDF) has been meeting on a regular basis since its formation and has contributed greatly to the Codex process, both through its development of drug residue standards and its illumination of the need to clarify that Codex decisionmaking must be based on science.
Veterinary drug residue standards are proposed to the CCRVDF by the FAO/WHO Joint Expert Committee on Food Additives (JECFA). The JECFA recommends an acceptable daily intake (ADI) and a maximum residue limit (MRL) for a veterinary drug residue in a specific food commodity. An MRL is essentially equivalent to a "tolerance," which is the term used in the U.S. The CCRVDF can either accept, reject, or modify the recommendations of the JECFA and makes a decision whether to forward the draft standard through the Codex Step procedure. The CCRVDF first considers the draft standard at Step 4. If the Committee decides to advance the draft standard, it will be forwarded to the Codex Alimentarius Commission for adoption at Step 5. If the Commission reacts positively to the draft standard, it is then returned to the CCRVDF for consideration as a final draft at Step 7. Final adoption takes place by the Commission at Step 8 when the draft standard is forwarded from the Committee in final form.
This process is very time-consuming. Although the CCRVDF has been meeting regularly since 1986, the first standards for veterinary drug residues in food were not adopted by the Commission until 1993. This delay stems from the controversial nature of the first standards developed by the CCRVDF, those for the growth-promoting hormones. In fact, although these standards were first presented to the Commission for adoption at Step 8 in 1991, final adoption did not occur until the Commission meeting in July 1995.
Standards for the following compounds were adopted at Step 8 (final stage) at the 20th and 21st Sessions of the Codex Alimentarius Commission:
Albendazole
Benzylpenicillin
Carbadox
Closantel
Estradiol 17-B
Flubendazole
Isometamidium
Ivermectin
Oxytetracycline
Progesterone
Sulfadimidine
Testosterone
Thiabendazole
Trenbolone Acetate
Zeranol
In the National Performance Review on Reinventing Food Regulations released in January 1996, FDA and FSIS committed to develop proposed procedures within one year on the review of Codex standards for consideration for acceptance. Currently, FDA only has procedures in place for review of Codex food commodity standards. FDA decisions to accept Codex standards will include the opportunity for public review and comments, especially if a need is identified to revise or revoke existing U.S. requirements. Finalized procedures would allow CVM to make decisions on the acceptance of Codex veterinary drug residue standards, for the purposes of imported food commodities and/or domestic food production.
The National Performance Report also highlighted the need to develop a procedure to allow acceptance of Codex standards when no approval for the drug exists in the U.S. The acceptance of this type of Codex standard would only apply to imported food commodities. Use of the drug in the U.S. would still require the filing and approval of a new animal drug application. FDA is supportive of legislative change to address this problem.
Finally, the U.S. believes that the scientific basis of Codex standards must be enhanced. This issue was outlined in the U.S. Codex Strategic Plan and continues to be a focus of U.S. efforts in Codex. The U.S. is not suggesting that Codex has not utilized good science in the past; however, we believe that certain changes are needed to make the scientific basis of the standards clear, consistent, and transparent. Examples of these changes would be to encourage FAO/WHO to establish minimum data sets for JECFA/JMPR, to establish criteria for selecting experts for expert groups and to make vacancies publicly available, and to assure clear and adequate documentation of the basis for decisionmaking on each standard. The U.S. believes that these changes are necessary to pave the way for greater acceptance of Codex standards in the U.S.
These ongoing harmonization efforts, undoubtedly, will impact on the trade of meat and meat products in the future. The adoption of Codex MRLs for veterinary drug residues by member countries of the Codex Alimentarius Commission will benefit animal producers in exporting worldwide.
This issue of the FDA Veterinarian contains the fifth in a series of questions and answers that are frequently asked about CVM's Veterinary Adverse Drug Experience (ADE) program.
Q. Why should veterinarians in practice care about reporting an ADE?
A. Veterinarians in practice depend on the information available in drug labeling to make informed choices about the risks and benefits associated with the use of a drug. The purpose of ADE monitoring is to ensure that animal drug labeling is adequate and accurate.
In spite of the highest standards for safety and effectiveness that exist for FDA approval, not everything is known about a drug when it is first marketed. Due to the limited size and controlled nature of premarketing clinical trials, only the most common adverse events will be observed and included in product labeling at the time of FDA approval. An accurate safety profile emerges only after a product is marketed and the number and spectrum of animals receiving the drug increases.
As a practicing veterinarian, you are in a unique position to observe adverse clinical outcomes associated with the use of drug products. Some of these problems may only be associated with extra-label drug use. You can assist in the development of a complete safety profile by reporting adverse experiences. Such reports are often the first signal that a problem exists. By participating in the reporting program and contributing to our knowledge of animal drugs, you provide a valuable service to animals, the public, and your colleagues in the veterinary profession.
Q. Where can I obtain information for a specific drug concerning potential adverse reactions?
A. The drug manufacturer is usually the best source for this type of information. Other sources include the FDA Center for Veterinary Medicine, the FDA/CVM Internet World Wide Web server (http://www.cvm.fda.gov/), the National Animal Poison Control Center and veterinary computer networks, such as VIN (America Online) and NOAH (Compuserve).
CVM ISSUES LETTER TO VETERINARIANS ON FLUOROQUINOLONES
On March 25, 1996, CVM issued a letter to bovine, swine, and poultry veterinary practitioners, advising them of their responsibility as part of the public health community regarding the use of fluoroquinolones. The FDA recently approved sarafloxacin (Saraflox 7 WSP and Injection) for use in broiler chickens and growing turkeys for the control of morbidity associated with Escherichia coli organisms. This is the first fluoroquinolone approved for use in food-producing animals. Enrofloxacin (Baytril 7) is approved for use in dogs and cats.
Experts acknowledge that the use of fluoroquinolones in animals may facilitate the emergence of bacterial resistance. When this occurs in enteric pathogens, the potential for transfer to humans exists, especially through food. Cross-resistance occurs throughout this entire class of drugs; therefore, resistance to one fluoroquinolone would compromise the effectiveness of all fluoroquinolone drugs. Evidence from some European researchers indicates that quinolone-resistant bacteria, particularly Campylobacter jejuni and some strains of Salmonella, are emerging in treated animal populations. The use of fluoroquinolones in food-producing animals is of particular concern to the human medical community because these drugs are used to treat a variety of infectious conditions. Practitioners are asked to do their part in preventing possible resistance by avoiding unnecessary or inappropriate treatment of animals with these drugs. Their cooperation is vital to ensure the continued availability of these products.
AVMA President-Elect Addresses CVM
by Linda A. Burgos, D.V.M.
On May 30, 1996, the Center for Veterinary Medicine (CVM) hosted a symposium sponsored by the CVM Training Committee. The invited speaker was American Veterinary Medical Association (AVMA) President-Elect, Mary Beth Leininger, D.V.M.
Dr. Leininger highlighted the attributes of the veterinary medical profession and emphasized the importance of the profession to the general well-being of humans as well as animals. She spoke of the new atmosphere at the AVMA to focus on serving the needs of its members. Dr. Leininger discussed the various tasks facing the AVMA such as representing the veterinary profession to the world, and providing a network to connect all of the diversities within the profession.
Dr. Leininger informed the seminar attendees about ways to access the AVMA. She discussed how to get questions answered, how to get action from the AVMA, how to get scientific articles published in the organization's two journals, and how to get involved in the AVMA. Dr. Leininger emphasized the availability and willingness of the AVMA staff members answering the telephones to assist veterinarians. Dr. Leininger even offered her voice mail telephone number and electronic mail address followed by a sincere invitation for veterinarians to use these means to contact her. Dr. Leininger may be reached at the AVMA by calling 1-800-248-2862, Extension 318. Her e-mail address is 74232.1150@compuserve.
Dr. Leininger responded to questions from the audience. She addressed issues such as the increasing legal value of companion animals, pet health insurance and third party payment of animal health care, and the roles of the AVMA President. Dr. Leininger cited the roles of the AVMA President as being chief spokesperson for the organization and the primary public relations person for the veterinary medical profession. Her goals for her term as AVMA President are to re-emphasize the importance of AVMA members and provide for their needs. The symposium concluded with closing remarks by Center Director Stephen F. Sundlof and presentation of a certificate of appreciation to Dr. Leininger.
PROPYLENE GLYCOL NOT GRAS FOR CAT FOOD
In the May 2, 1996 Federal Register, FDA published a final rule which excludes from generally recognized as safe (GRAS) status the use of propylene glycol in or on cat food. This final action is based on FDA's review of currently available information which has raised significant questions about the safety of this use. Further information on this regulation is available from Dr. David A. Dzanis, Center for Veterinary Medicine (HFV-222), FDA, 7500 Standish Place, Rockville, MD 20855.
In the April 29, 1996 Federal Register, FDA announced the availability of a revised guidance document entitled "Target Animal Safety and Drug Effectiveness Studies for Anti-Microbial Bovine Mastitis Products." The guidance document interprets statutory and regulatory requirements and outlines general procedures for conducting evaluations for anti-microbials being considered for approval. Further information on this document is available from Dr. Naba K. Das, Center for Veterinary Medicine (HFV-133), FDA, 7500 Standish Place, Rockville, MD 20855.
In the May 24, 1996 Federal Register, FDA announced the availability of a revised guidance document entitled "Bioequivalence Guidance, 1996; Availability." The guidance is intended to assist sponsors of new animal drug applications in the design and analysis of in vivo bioequivalence studies. Further information on this document is available from Dr. Melanie R. Berson, Center for Veterinary Medicine (HFV-135), FDA, 7500 Standish Place, Rockville, MD 20855.
Copies of both of these guidance documents are available from the FDA Veterinarian. Please send two self-addressed adhesive labels to assist in processing your request. In addition, written comments on these guidance documents may be submitted at any time to the Dockets Management Branch (HFA-305), Food and Drug Administration, 12420 Parklawn Drive, Room 1-23, Rockville, MD 20857.
MINOR SPECIES WORKSHOP TO BE HELD
FDA/CVM and the USDA/CSREES National Research Support Project Number 7 (NRSP-7) are sponsoring a workshop titled "Drug Availability for Minor Species in the 21st Century."
The Minor Use Animal Drug Program has been working since 1982 to develop the necessary data to obtain drug approvals for minor species. The changing regulatory and economic situation offers challenges and opportunities to fill the increasing need for minor use drugs. The incentives for development of these drugs are few, and the impact of the Animal Medicinal Drug Use Clarification Act of 1995 (AMDUCA) is unclear.
NRSP-7 and FDA/CVM are drawing together advocates and critics of schemes for providing drugs for these minor indications in a workshop to be held September 12-13, 1996 at the Holiday Inn, Bethesda, Maryland. It will feature a series of speakers to focus attention on various species, i.e., sheep and goats, veal calves, deer, game birds, ratites, zoologic species, aquaculture, ornamental fish, rabbits, and llamas. In addition, there will be representatives from the pharmaceutical industry to address their concerns and problems. The format will include small integrated groups to formulate priorities and strategies to move into the next century. The main goal of the workshop is to allow interaction with various groups and discuss priorities and problems encountered.
For further information or an agenda, please contact Dr. Alistair Webb, P. O. Box 100144, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0144, 352-392-4700 x3828.
by Ruth Reardon
The following firms/individuals received warning letters for offering animals for slaughter that contained illegal drug residues:
These violations involved illegal residues of penicillin in cull cows, residues of tetracycline in a cull calf, and residues of neomycin and penicillin in a bull calf.
The following firms received warning letters for deviations from the Good Manufacturing Practice (GMP) regulations:
NOTICE ON DIETARY SUPPLEMENT PRODUCTS
In the April 22, 1996 Federal Register, FDA published a notice regarding the inapplicability of the Dietary Supplement Health and Education Act of 1994 (the DSHEA) to products intended for use in animals. The notice states that after examining the statutory language, intent, and legislative history, the Agency has determined that DSHEA does not apply to animal products. Further information on this notice may be obtained from Donny Dean, Center for Veterinary Medicine (HFV-236), FDA, 7500 Standish Place, Rockville, MD 20855. Written comments on this notice may be submitted by July 22, 1996 to the Dockets Management Branch (HFA-305), Food and Drug Administration, 12420 Parklawn Drive, Room 1-23, Rockville, MD 20857.
WITHDRAWAL OF NOOH ON MFA PROPOSAL
In the May 15, 1996 Federal Register, FDA published a notice withdrawing a notice of opportunity for hearing (NOOH) on a proposal to withdraw approval of 11 medicated feed applications (MFA's) held by Benton County Ag Center, Inc. CVM has determined that the firm is in compliance with current good manufacturing practice regulations for medicated animal feeds and has instituted a system to maintain its compliance status. Further information on this notice is available from Karen A. Kandra, Center for Veterinary Medicine (HFV-246), FDA, 7500 Standish Place, Rockville, MD 20855.
Lloyd, Inc.
(NADA 140-994)
Generic and (Brand) Names
Tolazoline hydrochloride injection (Tolazine Injection)(TM) Rx
Indications
Horses. To reverse the effects of sedation and analgesia caused by xylazine.
Routes/Remarks
INJECTABLE: Each milliliter of sterile aqueous solution contains tolazoline hydrochloride equivalent to 100 milligrams of base activity.
Federal Register 5/23/96.
Hoechst-Roussel Agri-Vet Co.
(NADA 140-918)
Generic and (Brand) Names
Halofuginone hydrobromide and bambermycins.
Indications
Turkeys. For prevention of coccidiosis and for increased rate of weight gain in growing turkeys.
Routes/Remarks
MEDICATED FEED: Provides for use of approved Stenorol ® (2.72 grams of halofuginone hydrobromide activity per pound) and approved Flavomycin ® (4 and 10 grams of bambermycins activity per pound) Type A medicated articles to make Type C medicated feeds containing 1.36 to 2.72 grams of halofuginone hydrobromide and 2 grams of bambermycins per ton.
Federal Register 5/16/96.
Orion Corp. ORION --FARMOS (formerly Orion Corp. FARMOS)
(NADA 140-999)
Generic and (Brand) Names
Medetomidine hydrochloride injection (Domitor ®) Rx
Indications
Dogs. For use as a sedative and an analgesic in dogs over 12 weeks of age to facilitate clinical examinations, clinical procedures, minor surgical procedures not requiring muscle relaxation, and minor dental procedures not requiring intubation.
Routes/Remarks
INJECTABLE : Provides for use of 750 micrograms intravenously or 1,000 micrograms intramuscularly per square meter of body surface.
Federal Register 5/9/96.
Hoechst-Roussel Agri-Vet Co.
(NADA 140-919)
Generic and (Brand) Names
Halofuginone hydrobromide (Stenorol ®) and bacitracin methylene disalicylate (BMD ®)
Indications
Turkeys. For prevention of coccidiosis and for increased rate of weight gain in growing turkeys.
Routes/Remarks
MEDICATED FEED: Provides for use of approved Stenorol ® (2.72 grams of halofuginone hydrobromide activity per pound of Type A article) and approved BMD ® (30, 50, or 60 grams of bacitracin methylene disalicylate per pound) to make Type C medicated turkey feeds containing 1.36 to 2.72 grams per ton of halofuginone hydrobromide and 10 to 50 grams per ton bacitracin methylene disalicylate).
Federal Register 5/9/96.
Company
I.D. Russell Co. Laboratories
(NADA 6-891)
Generic and (Brand) Names
Sodium sulfaquinoxaline solution (Liquid Sul-Q-Nox)
Indications
Chickens, Turkeys, Calves, and Cattle. For use in chickens and turkeys as an aid in the control of outbreaks of coccidiosis and as an aid in control of acute fowl cholera. In calves and cattle for control and treatment of outbreaks of coccidiosis.
Routes/Remarks
Routes/Remarks
DRINKING WATER: Provides for 34 percent Liquid Sul-Q-Nox in drinking water. Also, the regulations are amended to codify a tolerance for sulfaquinoxaline residues in edible tissues of chickens, turkeys, calves, and cattle.
Federal Register 5/15/96.
Elanco Animal Health, Division of Eli Lilly and Co.
(NADA 95-735)
Generic and (Brand) Names
Monensin
Indications
Pasture Cattle weighing less than 400 lbs. For increased rate of weight gain.
Routes/Remarks
MEDICATED BLOCKS: Provides for use of monensin Type A medicated articles to make monensin Type C medicated feeds containing 25 to 400 grams per ton monensin as monensin sodium to be fed at 50 to 200 milligrams per head per day to pasture cattle (slaughter, stocker, feeder, and dairy and beef replacement heifers) weighing less than 400 lbs.
Federal Register 5/15/96.
Moorman Manufacturing Co.
(NADA 115-581) and Farmland Industries
(NADA 118-509)
Generic and (Brand) Names
Monensin
Indications
Pasture Cattle weighing less than 400 lbs. For increased rate of weight gain.
Routes/Remarks
MEDICATED FEED: Provides for free-choice feeding of monensin blocks.
Federal Register 5/15/96.
Merck Research Labs., Division of Merck & Co., Inc.
(NADA 140-971)
Generic and (Brand) Names
Ivermectin with pyrantel pamoate (Heartgard-30 ® Plus)
Indications
Dogs. For prevention of canine heartworm disease and for treatment and control of ascarid and hookworm infections.
Routes/Remarks
ORAL: Provides for extending the use of Heartgard-30 ®Plus to dogs weighing less than 5 lbs. In addition, the limitation in the regulation "Not to be used in dogs under 6 weeks of age" is being corrected to read, "Recommended for dogs 6 weeks of age and older."
Federal Register 4/5/96.
|
||||||
 |
||||||
|
||||||