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U.S. Food and
Drug Administration
FDA Consumer magazine
September-October 2002
Table
of Contents
By Linda Bren
Each October, when the mountain wind begins to carry a hint of winter chill, Lyle Johnston of Rocky Ford, Colo., loads hundreds of wooden boxes containing a special cargo onto flatbed trucks. He wants those trucks and their valuable cargo--30 million honeybees per truck--to be well down the road and on their way to California before the season's wintry blasts sweep through the Rockies.
The bees are destined to be put to work pollinating the almond fields of California, the source of more than half of the world's almonds. Johnston relies on the almond industry, and the almond industry relies on him and his fellow beekeepers. "Without the bees, the growers get only 300 to 400 pounds of almonds per acre," says Johnston. "With good hives, they get 2,200 to 2,800 pounds per acre."
American farmers rent honeybees to pollinate almonds, apples, melons, and more than a dozen other crops, raising the value of agricultural production by more than $14 billion per year, say entomologists at Cornell University.
Even so, the honeybee industry is dwindling. "It's a tough game right now," says Johnston, a third-generation beekeeper whose grandfather started the business in 1908. Bees are declining in number, largely because of the destructive efficiency of parasitic mites and American foulbrood, a bacterial disease that infects the young bee larvae and is killing off bee colonies across the nation.
Currently, there are no drugs approved by the Food and Drug Administration to treat the blood-sucking Varroa mites or the suffocating tracheal mites, and the one FDA-approved drug to treat American foulbrood is more than 40 years old. "Consequently, the bacteria have become resistant to treatment across large parts of the United States," says Mark Feldlaufer, Ph.D., research leader at the U.S. Department of Agriculture's (USDA) Bee Research Laboratory in Beltsville, Md.
But through the efforts of the Beltsville Bee Research Lab, the FDA, and a national research program called the USDA Minor Use Animal Drug Program, two more antibiotics to treat foulbrood may soon be available, and studies of a drug to treat Varroa mites will soon begin.
Despite their importance to agriculture, bees are considered a "minor species," and drugs to treat them are included in a category known as "minor use" drugs. There are few FDA-approved drugs available for minor use, but efforts to increase their number are being pursued on two fronts: through new legislation and through research partnerships. These partnerships among government agencies, minor species animal interest groups, universities, public hatcheries, and pharmaceutical companies are producing the data needed to support drug approvals.
A minor species is any animal species other than cattle, horses, pigs, chickens, turkeys, dogs, and cats, which are classified as major species.
Minor species include a wide variety of land animals such as sheep, goats, game birds, deer and elk, bison, emus, ostriches, rabbits, free-ranging wildlife, and zoo animals. They also include birds, ferrets, guinea pigs, and reptiles that are kept as pets. Aquatic animals, such as finfish, turtles, crustaceans, and mollusks, also qualify as minor species.
In addition to treating minor species, minor use drugs can also refer to those used in a major species to control a disease that occurs infrequently or in limited geographic areas. An example of a minor use in a major species is a drug to treat the parasitic infection babesiosis in dairy cattle in tropical regions of the United States.
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Minor Use and Minor Species Animal Health Act |
|
|---|---|
| 1996 | Congress passes Animal Drug Availability Act (ADAA) that requires the FDA to propose ways to improve the availability of drugs for minor uses and minor species. |
| 1997 | The FDA seeks public comment on documents including "Discussion Draft: Proposals to Increase the Availability of Approved Animal Drugs for Minor Species and Minor Uses" |
| 1998 | The FDA concludes federal statutes should be amended in report "Proposals to Increase the Legal Availability of Animal Drugs for Minor Species and Minor Uses" |
| 1999-2000 | MUMS Coalition established; uses FDA proposals and technical assistance to develop draft legislation |
| 2001 | The Minor Use and Minor Species Animal Health Act is introduced in Congress, but doesn't pass. |
| 2002 | The Minor Use and Minor Species Animal Health Act is reintroduced in Congress |
Only one or two drugs a year, on average, are approved for minor species, says Meg Oeller, D.V.M., the FDA's liaison to the USDA Minor Use Animal Drug Program. "It's a small number compared to the need."
But this number could increase with passage of the Minor Use and Minor Species Animal Health Act, known as the MUMS bill. In response to a congressional mandate under the 1996 Animal Drug Availability Act, the FDA proposed legislative and regulatory changes to improve the availability of drugs for minor uses. Building upon these FDA proposals and with the FDA's technical assistance, a coalition of animal health groups drafted the MUMS bill.
The bill would create a program similar to the FDA's human orphan drug program, which has dramatically increased the availability of drugs to treat rare human diseases. The human program encourages drug companies to seek approval of drugs for rare human diseases and conditions by offering companies help with study design and by giving financial incentives, such as tax relief, grants, and extended periods of marketing exclusivity. Similar incentives might encourage animal drug developers.
The MUMS bill also would provide the FDA some options such as conditional approval when reviewing drugs for minor uses. However, "The bill does not circumvent the need for public health and animal safety standards to be met," says Randy MacMillan, Ph.D., chairman of the MUMS Coalition and president of the National Aquaculture Association. "It would still have the mechanisms in place to address antibiotic resistance concerns, public safety concerns, and environmental concerns."
The MUMS bill was introduced in Congress in 2001 and again in 2002. "We continue to work with ... congressional people to get the MUMS bill passed as expeditiously as possible," says MacMillan.
Drugs to treat minor species used in agriculture are getting a boost from the Minor Use Animal Drug Program. This USDA program, officially known as National Research Support Project No. 7 (NRSP-7), funds and oversees many of the costly studies required to obtain FDA approval of an animal drug. The results of these studies are made public, and a drug company can then use them without cost to complete the process of applying to the FDA for drug approval. Once approved, the drug can be labeled, marketed, and made available for minor use.
The Minor Use Animal Drug Program works through the cooperation of many organizations. A drug manufacturer agrees to sponsor the drug; state agricultural research services, universities, and veterinary schools conduct studies; animal producers do field testing; and the FDA's Center for Veterinary Medicine (CVM) advises on the requirements needed for drug approval and reviews study results and other data.
Most of the program's efforts involve drugs already approved in a major species. For example, a drug approved for cattle may be studied for its safety and effectiveness in sheep. "With the sponsoring drug company's consent, we can use their toxicology and other data so we don't have to duplicate studies," says Stephen F. Sundlof, D.V.M., Ph.D., director of CVM. "This reduces some of the data requirements and saves a tremendous amount of money."
The program prioritizes and selects projects from requests made by animal producers, veterinarians or researchers. Current funding allows for about 1 in 6 requests to be researched.
The continued shortage of minor use drugs not only poses a serious threat to the health of animals--it also may set in motion a chain of events that could adversely affect nearly every American.
First, American farmers could find their livelihoods threatened, since unhealthy animals create significant losses to producers. Second, the American economy could face a worsening trade deficit, since more food animal products would need to be imported to make up for the loss. And third, American consumers could be exposed to a poorer quality of some imported food, since certain animal products originate in countries whose safety and environmental laws may be less stringent than U.S. standards.
So why the shortage of minor use drugs? "There is no economic incentive for pharmaceutical companies to get approval for these drugs since they affect a small population," says Sundlof. "Companies may feel that the size of the market doesn't justify the drug development costs."
Animal drugs must be approved for each species they are intended to treat. Just to add a new species to the label of an existing drug costs $2 million to $8 million. To get a brand-new drug approved, it costs a drug company an estimated $20 million and 8 to 10 years of concentrated research efforts.
Fish farming, or aquaculture, is one of the fastest growing segments of American farming, says the USDA. Yet to satisfy America's taste for seafood, the United States imports over $9 billion worth of fish each year--more than three times as much as it exports.
"The task for domestic producers is to supply a superior quality product at a reasonable cost," says MacMillan. "What the U.S. aquaculture industry needs is improved health-management systems. We need more vaccines and we need to be able to prevent infectious diseases. In the interim, we need methods to treat sick fish."
The USDA estimates losses of more than $100 million each year, attributable to 50 different fish diseases.
Aquaculture organizations and government agencies are investing heavily in drug research to help ease future losses to industry. The International Association of Fish and Wildlife Agencies, U.S. Fish and Wildlife Service, U.S. Geological Survey, USDA Minor Use Animal Drug Program, and commercial aquaculture operations are among those working in partnership to increase the availability of treatments for fish diseases.
Japan, a major seafood producer, has more than two dozen drugs or combinations of drugs approved for use in its aquaculture industry, according to the American Veterinary Medical Association. The United States has just six drugs approved for use in food fish.
"Water quality in many developing countries is not as good as ours," says Roz Schnick, who helps producer groups and pharmaceutical and chemical companies work together to gain drug approvals. "This creates more stress on the animals, and with stress comes disease so they have to use more drugs," says Schnick. "In the United States, we don't need a lot of drugs--just a basic medicine chest that we are currently attempting to achieve through proper approval procedures."
Schnick reports that through the efforts of federal and state government agencies and a consortium of aquaculture organizations, the medicine chest will soon fill up--four new aquatic animal drug applications and two supplemental applications are close to being submitted to the FDA for approval.
Additional aquaculture drug research may be expedited through "species grouping." In aquaculture, where there are hundreds of species, it is not practical to test a drug on all of them, says the FDA's Oeller. Researchers are trying to group similar species of fish in order to test drug effectiveness, safety in target animals, and safety in human food. This grouping may yield representative species whose data can be used to support including similar species on the label of a new animal drug.
Fish are not the only animals that can benefit from species grouping research, says Oeller. Other groups may include game birds (pheasants, partridges, quail), deer (white tail, red deer, elk), and ratites (ostriches, emus). "It may be that the research will show that the species are not similar, or are not similar for some classes of drugs," says Oeller. "Learning what is and is not suitable for grouping will be very valuable in making drug approval for minor species more efficient."
Although much of its minor species research centers on aquatic animals, the Minor Use Animal Drug Program also is investigating the needs of other animals used in agriculture. Some of this research is motivated by the needs of American farmers seeking healthful alternatives to the traditional red-meat market.
Meats from ostriches, emus, bison, deer, and elk have some nutritional benefit over other red meats, according to a USDA-funded study conducted at the University of Wisconsin-Madison. "These alternative meats, like traditional meat and poultry, are high in protein," says Dennis Buege, Ph.D., lead study researcher. "Their cholesterol content is similar to the other meats and poultry. However, they tend to be lower in fat than beef, pork and dark meat chicken, and higher in iron than beef, pork, and light and dark meat chicken." (See "How Meats Measure Up.")
The Minor Use Animal Drug Program has conducted research to support the approval of a drug for bison, and several projects are in progress for deer and elk. As yet, there are no drugs approved to treat flightless birds known as ratites, but the program recently has received several requests from this growing industry.
The program is researching treatments for diseases in sheep and goats, also minor species. A number of drugs to treat these animals have been approved, but more are needed, particularly to aid America's declining sheep industry.
| Nutrients | Daily Dietary Rec.1 |  |
 |
 |
 |
 |
 |
 |
|
 |
|---|---|---|---|---|---|---|---|---|---|---|
| Ostrich2 (top loin) |
Emu (loin) |
Venison (loin) |
Bison (sirloin) |
Elk (rib/loin) |
Beef3 (loin) |
Chicken3 (breast) |
Chicken3 (thigh) |
Pork3 (loin) |
||
| Calories (kcal) | 1600-2800 | 132 | 123 | 128 | 146 | 141 | 182 | 140 | 178 | 173 |
| Protein (gm) | 50 | 24 | 25 | 26 | 24 | 26 | 29 | 26 | 22 | 26 |
| Total Fat (gm) | <65 | 3.3 | 2.7 | 2.0 | 4.8 | 3.3 | 8.6 | 3.0 | 9.2 | 6.6 |
| Saturated Fat (gm) | <20 | 1.0 | 0.7 | 1.0 | 2.1 | 1.6 | 3.3 | 0.9 | 2.6 | 2.3 |
| Cholesterol (mg) | <300 | 79 | 75 | 67 | 73 | 64 | 65 | 72 | 81 | 68 |
| Iron (mg) | males:
8 females: 18 |
2.8 | 4.3 | 3.5 | 3.0 | 3.4 | 2.1 | 0.9 | 1.1 | 0.7 |
|
(gm=grams, mg=milligrams,
kcal=kilocalories) (Source: Dennis Buege, Ph.D., University of Wisconsin-Madison, and Juliet Howe, Ph.D., USDA Nutrient Data Laboratory) |
||||||||||
The U.S. sheep population has been steadily decreasing since the 1940s--from its peak at 56 million in 1942 to less than 7 million in 2002, says the USDA.
The lack of approved drugs for sheep is one factor contributing to the decline, says Oeller. The sheep industry loses about $45 million worth of sheep each year from diseases for which drugs are unavailable.
In addition to disease-treating drugs, American sheep ranchers are lacking another important tool: "the capability to manipulate reproduction," says Oeller. In other countries, such as Australia, sheep ranchers can use progesterone implants to manipulate the reproductive cycle. "This gives them spring and fall breeding of sheep, while we are limited to one breeding season in this country," says Oeller.
In response to the industry's need, the Minor Use Animal Drug Program is currently researching a vaginal progesterone for sheep and goats.
Powell Anderson, D.V.M., splits his time between his veterinary hospital in Dillwyn, Va., and his ostrich ranch next door. An ostrich breeder since 1996, Anderson sees the future of agriculture and the rebirth of small farms in businesses like his. It's a healthy and environmentally sound alternative to some other forms of animal food production, says Anderson, who doesn't use growth hormones or antibiotics in his birds.
Anderson sells the low-fat ostrich meat, which he compares to filet mignon in taste, to local restaurants. He incubates the fertile eggs during mating season and sells them for food in the mating off-season. "You can't taste the difference between scrambled ostrich eggs and chicken eggs," says Anderson, who plans to be eating ostrich eggs for a very long time. "The females lay eggs for 40 years and live to be 70."
With no FDA-approved drugs to treat ostriches, Anderson must rely on his own knowledge of veterinary medicine, an ostrich encyclopedia, and trial and error. Luckily, his birds have been pretty healthy, he says, but when one is sick, it goes down quickly. "You can't tell they're sick until they're almost dead."
Sharyn Felts, owner of one of the largest emu ranches in California, also considers herself blessed that most of her 800 emus have been disease-free. The six-foot tall, 150-pound birds, second in size only to ostriches, are very hardy, she says.
In addition to their meat, the emus are valued for their oil as an emollient used in moisturizers, shampoos and soaps. Their feathers are used by fishermen to tie flies, and their hides serve the leather industry. The dark green emu eggs are prized by artists, who carve or paint them.
The Animal Medicinal Drug Use Clarification Act (AMDUCA) of 1994 eased the scarcity of animal drugs somewhat by allowing veterinarians to use approved animal and human drugs "extra-label," or "off-label." This means that under certain circumstances, veterinarians can use drugs approved for other species, for other diseases and conditions, or at different dosage levels from those listed on the drug label.
This flexibility of drug use may help to ease animal suffering, but the different metabolisms of some species make the effective dosage a guessing game, says Oeller. The benefit of having a drug approved for a specific species is that "you can count on a specific withdrawal time and know the correct dosage," Oeller says.
Although the AMDUCA allows off-label use of drugs, it prohibits off-label use in animal feed. But medicated feed often is the best route of getting a drug into certain animals, such as fish and game birds. Injecting an individual fish with a drug may be feasible for some types of brood stock, says MacMillan. "But such injection is not feasible for a large population of farm-raised aquatic animals such as trout, catfish, tilapia or bait fish."
Bill Mac Farlane, who owns one of the nation's largest pheasant farms, located in Janesville, Wis., says he needs medicated feed for his pheasants and other game birds, particularly to treat coccidia, a deadly parasite that infests the intestines. The alternatives to medicated feed don't work very well, says Mac Farlane. It's not practical to catch each bird and give them a shot every day, nor is adding a drug to the water effective. "They don't like the taste of the medicated water. They drink out of the puddles after a rain instead, so they don't get their medication."
To meet the requirements of the fish and bird industries, the Minor Use Animal Drug Program has shifted much of its focus to the approval of medicated feeds, says Oeller. The program is currently testing several medicated feeds for pheasants to treat bacterial infections and coccidia and other parasites, and Mac Farlane's pheasant farm is participating in the study trials.
Currently, the Minor Use Animal Drug Program is working on more than two dozen projects, and continues to review requests for treatments to keep animals healthy. Among the active projects are drugs to treat diseases in game birds, goats, sheep, deer, rabbits, bees, and a variety of fish.
"It's never a good idea to have unhealthy animals," says Oeller. "You don't want the risk of products from unhealthy animals entering the human food supply, you don't want them exposing other agricultural animals to disease, and you don't want wildlife transporting disease-carrying ticks into areas frequented by people. Both from a public health and an animal welfare standpoint, you're better off having healthy animals."
For more information, visit the Minor Use Animal Drug Program Web site and the FDA Center for Veterinary Medicine Web site.
Few FDA-approved drugs are available for animals considered to be "minor species." These include wildlife, exotic animals, endangered species, and pets such as birds, rabbits, reptiles, and guinea pigs.
Veterinarians who treat these animals often must rely on unapproved animal drugs or drugs approved for humans or other animals. Sometimes a drug approved for one animal can be used with confidence in another animal with a similar metabolism, says Stephen F. Sundlof, D.V.M., Ph.D., the director of the FDA's Center for Veterinary Medicine. "But when it comes to exotic animals, there is no formula for extrapolating between one species and another--it's a big gamble."
More animal drugs could be available if the Minor Use and Minor Species Animal Health Act is passed by Congress. The "MUMS bill" would establish several new ways to lawfully market new animal drugs while maintaining the rigorous public safety requirements of the FDA.
-- L.B.