Considerations for Treating Minor Food-Producing Animals with Veterinary Pharmaceuticals

51
Considerations for Treating Minor Food-Producing Animals with Veterinary Pharmaceuticals


Lisa A. Tell, Margaret Oeller, Tara Marmulak, and Ronette Gehring


The Use of Veterinary Pharmaceuticals in Minor Food-Producing Animals: Special Considerations and Challenges


Antibiotics, antiparasitics, nonsteroidal antiinflammatory drugs, and exogenous hormones are among the essential components in the armamentarium of a food animal veterinarian to combat disease, alleviate animal pain, and minimize economic losses. In the United States, many of these veterinary products are US Food and Drug Administration (FDA) approved for use in a large number of major food-producing animals but not for the minor food-producing animals. According to the FDA, the major food-producing animals are cattle (meat and milk), swine, chickens (meat and eggs), and turkeys. The minor food-producing animals are those that do not fall into the major food-producing animal category with the most popular being goats (both dairy and meat), sheep, deer, commercially raised game birds, and food fish and shellfish. This category also includes less obvious food-producing species such as rabbits, ratites, and honey bees. In the USA, horses are a major animal species; however, they are considered companion animals and are not customarily used for human food as in some other countries. In Europe, the European Medicines Agency has defined the major food-producing animals to be cattle (meat and milk), sheep (meat); pigs; chickens (meat and eggs), and salmonids. Minor food-producing animals include minor ruminants (meat and milk), deer (including reindeer), other avian species (meat and eggs), other fish species, and other mammalian species (horse and rabbit). In other countries, the minor food-producing animal category has the potential to be considerably larger because a greater variety of species are consumed such as small rodents, canids, invertebrates, and various avian species.


In recent years, there has been an increased interest in consuming more meat and other products from minor food-producing animals, especially aquaculture species. As this interest grows, so will the expectations to provide safe food items for human consumption. Maintaining the overall health of minor food-producing animals is similar to managing the health of major food-producing animals, and typically requires some use of veterinary pharmaceuticals. However, in contrast to the major food-producing animals, few drugs have FDA approval for use in minor food-producing animals.


One of the major challenges for getting veterinary products approved for use in minor food-producing animals is the reduced economic return due to small market size. Additionally, some of the minor food-producing animals are less tractable (e.g., cervids and bison), and there is wide variation in breeds/species with respect to size and pharmacokinetics. In general, there is a large number of species and incredible diversity within this category. For aquatic species, such as finfish, mollusks, and crustaceans, not only are there species differences, but environmental considerations (salinity, pH, temperature), physiological differences (heterothermy), and management practices that also impact metabolism and excretion of drugs.


This chapter addresses the unique issues associated with the regulatory requirements for getting a drug approved for use in a minor food-producing animal, the availability of veterinary pharmaceuticals for use in minor food-producing animals, and highlights legislation that has helped address the veterinarian’s need for medications to treat these animals. In addition, government programs and scientific approaches used to meet the therapeutic needs for treating minor food-producing animals are discussed.


The Approval Process for Veterinary Pharmaceuticals for Use in Minor Food-Producing Animals


There are many veterinary pharmaceuticals marketed today that may be administered to minor food-producing animals. The ideal scenario for a veterinarian wanting to treat a minor food-producing animal is having an FDA-approved drug labeled for the intended use in question. One example would be an anthelmintic approved for treating specific gastrointestinal parasites in sheep. This product will have been demonstrated to FDA’s satisfaction to be safe for sheep, safe for the person administering the drug to the sheep, safe for anyone who later consumes meat from the treated sheep, and safe for the environment, both during the drug’s use and its disposal. It will also have been shown to be effective for the labeled use and that it is consistently manufactured to standards of strength and purity. Such a product is labeled with intended uses, doses, and withdrawal times that are appropriate for use in sheep.


In contrast to the major food-producing animals, there are not many FDA-approved drugs labeled for use in minor food-producing animals. This is mainly because the development of new drugs for use in animals is a very expensive and time-consuming process, especially for drugs to be used in animals intended for human consumption, and the minor food-producing animal markets are too small to readily recover the pharmaceutical sponsor’s investment. FDA-approved drugs for minor food-producing animals (as of July 2017) are summarized in Tables 51.151.5. There is also a searchable database of approved new animal drugs available on the FDA website. Please note that even if approved, a particular product may not be commercially available. This can be for a variety of reasons including closing of manufacturing facilities, or the discontinuation of less lucrative product lines when two companies merge.


Table 51.1 Veterinary pharmaceuticals approved by the Food and Drug Administration as of July 2017 for use in small ruminants that are considered minor food-producing animals in the United States of America














































































































































































Drug Formulation Species Indicationa
Albendazole Liquid suspension Sheep Internal parasites
                        Goats Liver flukes
Ceftiofur sodium Injection

Goats


Sheep

Respiratory infection
Chlortetracycline Premix (for feed) Sheep

Vibrionic abortion


Claim withdrawn

Decoquinate Premix (for feed)

Goats


Sheep

Coccidiosis
Fenbendazole Liquid suspension Goats Internal parasites
Fenbendazole Premix (for feed)

Zoo/wild goats


Bighorn sheep

Internal parasites
Flurogestone acetate Vaginal sponge Sheep Estrus synchronization
Follicle stimulating hormone Injectable—IV, IM, SQ Sheep FSH deficiency
Ivermectin Drench/liquid Sheep Internal parasites
Lasalocid Premix (for feed) Sheep Coccidiosis
Levamisole hydrochloride

Drench


Bolus


Powder

Sheep Internal parasites
Monensin sodium Premix (for feed) Goats Coccidiosis
Morantel tartrate Premix (for feed) Goats Internal parasites
Methoxyflurane Inhalation Sheep Anesthetic
Moxidectin Drench Sheep Internal parasites
Neomycin sulfate

Powder


Liquid


Goats


Sheep

Colibacillosis
Neomycin sulfate Premix (for feed) Sheep Colibacillosis
Neostigmine methylsulfate Injectable—SQ Sheep

Rumen atony


Curare antagonist

Oxytetracycline

Premix (for feed)


Powder

Sheep

Respiratory infection


Colibacillosis


Claim withdrawn

Oxytetracycline hydrochloride—Polymyxin B Sulfate Ointment Sheep Superficial ocular infections
Oxytocin Injection—IM, IV, SQ Sheep

Uterine contractions


Milk letdown

Penicillin G procaine Injectable—IM Sheep Respiratory infection
Pituitary luteinizing hormone Injectable—IV, SQ Sheep Pituitary hypofunction
Progesterone Intravaginal device (CIDR) Sheep Out-of-season breeding
Proparacaine hydrochloride Liquid Sheep Ophthalmic anesthetic
Sodium chloride gelatin Oral liquid Sheep Shock/hypovolemia
Sodium selenite/ Vitamin E Injectable—IM, SQ Sheep Selenium deficiency
Tetracycline Injectable—IM Sheep Bacterial infection
Thiabendazole

Drench


Premix (for feed)


Pellet


Liquid


Goats


Sheep

Internal parasites
Thialbarbitone sodium Powder—injectable IV Sheep General anesthetic
Tilmicosin phosphate Injection Sheep Respiratory infection
Zeranol Implant—SQ Sheep Weight gain/feed efficiency

aListed indications are broad. For specific indications, the drug label or Code of Federal Regulations should be consulted.


Table 51.2 Veterinary pharmaceuticals approved by the Food and Drug Administration as of July, 2017 for use in cervids/other ruminants that are considered minor food-producing animals in the United States of America





























Drug Formulation Species Indicationa
Ivermectin Injection

Bison (American)


Reindeer


Hypodermosis


Warbles


Diprenorphine hydrochloride


Etorphine hydrochloride

Injectable – IM, IV Wildlife Immobilization
Xylazine hydrochloride Injectable—IM, IV

Deer


Elk

Sedation
Yohimbine hydrochloride Injectable—IV

Deer


Elk

Xylazine antagonist

aListed indications are broad. For specific indications, the drug label or Code of Federal Regulations should be consulted.


Table 51.3 Veterinary pharmaceuticals approved by the Food and Drug Administration as of July, 2017 for use in avian species that are considered minor food-producing animals in the United States of America















































































Drug Formulation Species Indicationa
Amprolium Premix (for feed) Pheasants Coccidiosis
Bacitracin methylene disalicylate Premix (for feed)

Pheasants


Quail

Weight gain/feed efficiency
Bacitracin methylene disalicylate Water-soluble powder Quail Ulcerative enteritis
Bacitracin zinc Premix (for feed)

Pheasants


Quail

Weight gain/feed efficiency
Bacitracin zinc Water-soluble powder Quail Ulcerative enteritis
Carnidazole Tablets Pigeons Trichomoniasis
Chlortetracycline Premix (for feed) Ducks Fowl cholera
Iodinated casein Premix (for feed) Ducks Weight gain/feathering
Lasalocid Premix (for feed) Partridge (Chukar) Coccidiosis
Monensin sodium Premix (for feed) Quail (Bobwhite) Coccidiosis
Novobiocin Premix (for feed) Ducks Bacterial infection
Salinomycin sodium

Premix (for feed)


Powder

Quail Coccidiosis
Sulfadimethoxine ormetoprim Premix (for feed)

Ducks


Partridge (Chukar)


Bacterial infection


Coccidiosis

Thiabendazole Premix (for feed) Pheasants Gapeworm

aListed indications are broad. For specific indications, the drug label or Code of Federal Regulations should be consulted.


Table 51.4 Veterinary pharmaceuticals approved by the Food and Drug Administration as of May, 2014 for use in aquaculture species in the United States of America

























































































Drug Formulation Species Indicationa
Florfenicol Premix (for feed) Catfish Enteric septicemia of catfish
Florfenicol (now fully approved) Premix (for feed) Catfish Columnaris disease
Florfenicol Premix (for feed) Freshwater-rearedSalmonids

Coldwater disease


Furunculosis

Florfenicol Premix (for feed) Freshwater-reared finfish

Streptococcal septicemia


Columnaris disease

Formalin Water treatment

Finfish eggs


Shrimp (Penaeid)


Antiprotozoal


Antifungal

Human chorionic gonadotropin Injection Finfish (male and female broodstock) Spawning aid
35% Hydrogen peroxide Water treatment Freshwater-rearedSalmonids Bacterial gill disease
35% Hydrogen peroxide Water treatment Freshwater-reared finfish eggs Saprolegniasis
35% Hydrogen peroxide Water treatment Freshwater-reared cool water finfish and channel catfish External columnaris disease
Oxytetracycline dihydrate Premix (for feed) Lobsters Gaffkemia
Oxytetracycline dihydrate Premix (for feed) Salmonids Ulcer diseases
Oxytetracycline dihydrate Premix (for feed) Salmonids and catfish

Bacterial hemorrhagic septicemia and Pseudomonas disease

Oxytetracycline hydrochloride Water treatment Finfish Skeletal marking
Sulfadimethoxine ormetoprim Premix (for feed)

Catfish


Salmonids


Enteric septicemia of catfish


Furunculosis

Sulfamerazine Premix (for feed) Trout Furunculosis
Tricaine methanesulfonate Water treatment Fish Temporary immobilization

aListed indications are broad. For specific indications, the drug label or Code of Federal Regulations should be consulted.


Table 51.5 Veterinary pharmaceuticals approved by the Food and Drug Administration as of May, 2014 for use in miscellaneous minor food-producing animals







































Drug Formulation Species Indicationa
Lasalocid Premix (for feed) Rabbits Coccidiosis
Lincomycin hydrochloride Water soluble powder Honey bees American foulbrood
Oxytetracycline

Premix (for feed)


Water soluble powder

Honey bees American and European foulbrood
Sulfaquinoxaline Premix (for feed) Rabbits Coccidiosis
Tricaine methanesulfonate Water Treatment Amphibians Temporary immobilization
Tylosin tartrate Water soluble powder Honey bees American foulbrood

aListed indications are broad. For specific indications, the drug label or Code of Federal Regulations should be consulted.


For a drug to be approved for use in a minor food-producing animal, the sponsor must demonstrate to the satisfaction of the scientific reviewers at FDA’s Center for Veterinary Medicine (CVM) that it is safe and effective for its intended use. CVM is the component of FDA responsible for the regulation of veterinary drugs, including the evaluation of such drugs prior to approval.


The information that a sponsor needs to present to support a New Animal Drug Application (NADA) includes the following as outlined in regulations published in the Code of Federal Regulations (21 CFR 514):



  1. effectiveness for the proposed use;
  2. safety to the target animal species (the animal species for which the drug is to be used);
  3. human food safety (safety to consumers of meat, milk, or eggs derived from treated animals);
  4. environmental safety;
  5. manufacturing methods and controls;
  6. all other information;
  7. freedom of information (FOI) summary; and
  8. product labeling.

These components are discussed in detail in Chapter 55 of this book. The FDA also provides a variety of guidance documents to assist sponsors in understanding the various requirements. Of particular note for sponsors seeking drug approval for a minor species use is Guidance #61 FDA Approval of New Animal Drugs for Minor Uses and for Minor Species. This document is being revised at the time of writing this chapter and will be published under the new title, Special Considerations, Incentives, and Programs to Support the Approval of New Animal Drugs for Minor Uses and for Minor Species. Guidance documents are available on the FDA website.


Compared to the drug approval process for major food-producing animals, the drug approval process is not significantly easier for products intended for use in a minor food-producing species. The same high standards must be met. However, there are a few advantages afforded to products intended for use in a minor food-producing animal. These include the possibility of a waiver from user fees, the ability to apply conclusions reached from the radiolabeled residue study in the major food-producing animal to the human food safety evaluation for the minor food-producing animal, the possibility of a categorical exclusion from the need to provide an environmental assessment, and the possibility that fewer sites will be needed for effectiveness clinical trials.


Legislation and Policies Supporting the Availability of Veterinary Pharmaceuticals in Minor Food-Producing Animals


Animal Medicinal Drug Use Clarification Act


The US Congress recognized the drug availability problem for both major and minor animal species when it passed the Animal Medicinal Drug Use Clarification Act (AMDUCA) in 1994 (Public Law No. 103–396; Monti, 2000). This law addressed the fact that FDA generally approves veterinary drugs for narrow intended uses. For example, a broad-spectrum antibiotic that would be safe and effective for the treatment of a wide variety of bacterial infections may only be approved for use in cattle for the treatment of respiratory disease caused by specific bacteria. From a practical standpoint, the pharmaceutical sponsor cannot demonstrate safety and effectiveness for every possible intended use of the product. This means that veterinarians frequently administer the drug for indications that are not on the label. In other words, they use the drug for different diseases, at different doses, by different routes of administration, and in different animal species than what is indicated on the label.


AMDUCA legalized this practice for veterinarians within a set of limitations described in the Code of Federal Regulations (21 CFR 530). In general, veterinarians, within the context of a valid veterinarian–client–patient relationship, may use approved dosage form products (but not medicated feeds) outside their labeling. This is allowed only when there is no approved drug for the intended use; other approved drugs are not effective for such use, when the dose is not effective for that use, or in cases where an approved formulation is not appropriate. When using a drug outside of its labeling for a food-producing animal, the veterinarian is responsible for using the drug in a manner that will not result in a violative residue in any food product derived from that animal. The veterinarian must establish a withdrawal period based on some scientific information, although there are few resources for establishing such times. The withdrawal period may be based on data in published literature, extrapolated from the pharmacokinetic profile of the drug, or determined through consultation with organizations such as the Food Animal Residue Avoidance and Depletion Program (FARAD). There are also certain drugs not eligible for extralabel use in food-producing animals. These are listed in the CFR at 530.41. This list includes a fairly new ban on the extralabel use of most cephalosporins. This ban applies only to the major species – cows, pigs, chickens, and turkeys.


Compliance Policy Guide 615.115

Feb 8, 2018 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Considerations for Treating Minor Food-Producing Animals with Veterinary Pharmaceuticals
Premium Wordpress Themes by UFO Themes