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The Government Printing Office has informed us that the subscription price for the FDA Veterinarian has been increased to $8.50 per year domestic and $10.65 per year for foreign subscriptions. These price increases are due to increased costs of printing and mailing. While we regret that these increases were necessary, we believe that these prices still represent a good value for a newsletter full of information you can use right away. There is also good news in that credit card subscription orders now may be placed by telephone. These credit card orders can be made from 8 a.m. to 4 p.m. Eastern time to (202) 512-1800. Credit card orders can be faxed 24 hours a day to (202) 512-2250.
REGULATION OF ANIMAL ELECTRONIC IDENTIFICATION PRODUCTS
CVM has received a number of inquiries about how the Agency regulates implantable
electronic identification devices for use in animals. The following is an update
on this subject. This applies only to implantable electronic identification
products intended for the sole purpose of animal identification.
Implantable electronic identification device (EID) products that are used to identify individual animals are being developed by several companies. The products consist of a very small transponder which is implanted in the body of the animal (in the ear, for example), and a component (reader) that interprets the transmission from the transponder.
CVM supports the development and use of animal identification products....
CVM supports the development and use of animal identification products and believes that these products can produce benefits for livestock producers, the agricultural industry, regulatory agencies, and consumers. Proper identification of animals at slaughter makes possible traceback of the slaughtered animal to its source. This traceback greatly facilitates FDA's investigations to determine cause and responsibility when residues of drugs or chemical contaminants are found in edible tissue. Presently, FDA staff is working with manufacturers of implantable EID products to facilitate their availability.
Under the Federal Food, Drug, and Cosmetic Act (the Act), FDA may regulate implantable EIDs intended for use in animals as food additives. A food additive is defined by the Act as "any substance, the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming or otherwise affecting the characteristics of any food." Also, under the Act, food includes animal feed.
To ensure public health and the safety of the food supply, FDA has determined that EIDs must not be implanted in an edible portion of an animal unless a human food additive regulation for this use has been published. Noncompliance with this requirement would render the food product adulterated and subject to FDA regulatory action. Currently, no human food additive petitions have been approved for EIDs intended to be implanted in an edible portion of any animal, nor does FDA anticipate approving any of these types of petitions because of the kinds of component materials currently present in EIDs.
Nonedible portions of slaughtered animals are routinely rendered to become part of animal feed. Unless the implanted EID unit is removed and properly discarded prior to rendering, it likely will become part of animal feed. Therefore, implantable EID products that might become part of feed are regulated by FDA's Center for Veterinary Medicine (CVM) as animal food additives.
In some specific cases, CVM may exercise enforcement discretion and not take regulatory action against the use of an animal food additive that is not covered by a food additive regulation. With regard to EIDs intended for implantation in nonedible portion of animals (such as ears and ligaments), CVM may exercise its enforcement discretion and not take regulatory action if manufacturers provide safety information on each implantable model intended for marketing. The information must be adequate to assure that there are no human food safety concerns arising from the consumption of products (meat, milk, or eggs) from animals that have consumed feed containing rendered products with EID component material. Further, the information must be adequate to assure that there are no environmental concerns associated with the proposed use. If the human food safety and environmental safety concerns are satisfactorily addressed, the Agency will notify the manufacturer in writing that, as a matter of regulatory discretion, sale of the specific model EID may take place without an animal food additive regulation.
To assure that the implant will not enter human food, the implantation site should be in an area that will minimize potential for migration to edible tissue. The EID manufacturer must receive concurrence from U.S. Department of Agriculture (USDA) as to the acceptability of the implantation site(s).
At this time, there is no acceptable implantation site for swine. This is because all portions of the pig may be used for human food. An alternative for swine would be to incorporate the EID in a plastic ear tag that could be removed at slaughter.
CVM does not require data (human food safety or environmental safety) from firms marketing implantable EID products solely for pet animals (e.g., dogs, cats, pet birds), including horses that will not be used for food purposes, and laboratory animals. These products may be marketed at this time.
Questions about CVM's electronic identification device policy may be directed to Richard E. Jewell, CVM Division of Compliance, Case Guidance Branch, 7500 Standish Place, HFV-236, Rockville, MD 20855, or by calling (301) 594-1785.
FDA'S VIEW ON THE USE OF NON-TRADITIONAL PRODUCTS IN ANIMAL FEEDS
The following are excerpts from a presentation made by Daniel G. McChesney,
Ph.D., Leader of CVM's Feed Safety Team, at the Food Waste Recycling Symposium
held January 22 & 23, 1996, in Atlantic City, New Jersey.
FDA has primary responsibility in the Federal government for food safety in the United States. The Agency enforces the Federal Food, Drug, and Cosmetic Act (FFDCA), and food safety related aspects of the Public Health Service Act (PHSA). Under these Acts, FDA is responsible for ensuring that human foods and animal feeds are safe and, among other things, do not contain illegal residues of drugs, pesticides, environmental contaminants, or microorganisms, including mycotoxins and bacterial toxins, that are harmful to public health. The Department of Agriculture (USDA) is responsible for the safety of human food products resulting from the slaughter of food animals.
FDA has widespread responsibilities to help ensure preharvest food safety under these Acts. For example, one mission of FDA's Center for Veterinary Medicine (CVM) is to regulate the levels of contaminants permitted in animal feeds to ensure that the food for man and animals is safe and free of illegal drugs, industrial chemicals, pesticide residues, and harmful bacteria.
The FFDCA defines food as "articles used for food or drink for man or other animals . . . and articles used for components of any such article." Therefore, any waste product, garbage, by-product or co-product, regardless of source, that is intended to be used as a feed ingredient or becomes part of an ingredient or feed is considered a "food" under the FFDCA and thus subject to regulation. Furthermore, it is the position of FDA that a product intended for use as a feed or feed ingredient must not be adulterated as defined by Section 402 of the FFDCA. The Act has numerous provisions for establishing adulteration. The most appropriate subsections of the Act that apply to garbage, waste products, by-products and co-products state, in part, that a food (feed) shall be deemed to be adulterated "if it bears or contains any poisonous or deleterious substance which may render it injurious to health" and that "a food shall be deemed to be adulterated if it is otherwise unfit for food (feed)." Additionally, the FFDCA states that a food (feed or feed ingredient) can be considered adulterated if "it bears or contains any food additive which is unsafe (unapproved) with in the meaning of Section 409."
The definition of food and the regulations referred to above have important implications for companies or municipalities wishing to market garbage, waste products, by-products or co-products as an animal feed or feed ingredient. These companies or municipalities must realize that they are producing a food product and have an obligation to produce a safe and wholesome product. In order to be able to do this, they must consider the source, the ingredients, and the quality of the ingredients used in the principal product and ensure that these do not result in garbage, waste products, by-products or co-products that will cause the adulteration of the feed, feed ingredient or animal tissue, or human food.
The potential economic and resource conservation benefits for using non-traditional sources for animal feed ingredients and feed can be substantial. The variety of waste products, by-products and co-products that are being considered for use in animal feed is growing rapidly, and with improvements in processing technology and their application, the FDA anticipates even more rapid growth in the future. Government, whether it be Federal or State, cannot develop regulations rapidly enough to address each product and the nuances associated with it. Therefore, an approach that establishes basic safety requirements, product identity, and removes government as the quality control department for a company or municipality is needed. In the "traditional" animal feed industry, Federal and State governments have established regulatory guidance (tolerances, action levels) for safety related issues and the Association of American Feed Control Officials (AAFCO), has established definitions for product identity. Industry has the primary responsibility for quality assurance and producing an unadulterated product. Government's role is one of oversight to ensure that industry is fulfilling its role.
To address the quality assurance issue, FDA suggests that manufacturers implement a HACCP (Hazard Analysis Critical Control Points) program to address safety issues associated with their product.
FDA chose the HACCP approach because it is preventative and addresses the root causes of food safety problems including those associated with production, storage, and transportation. Furthermore, the HACCP approach requires the manufacturer to analyze, in a rational, scientific manner, its production processes in order to identify critical control points. Essential parts of industry's role under HACCP are to establish critical limits and monitoring procedures, and to maintain records documenting adherence to the critical limits related to the identified critical control points. Meeting these requirements results in continuous self-inspections by industry. Analysis and control is confirmed by government oversight of the industry's monitoring. As such, a HACCP-based approach provides an appropriate balance between the responsibilities of industry and government in ensuring food safety.
The following are examples of FDA's views on non-traditional products proposed for use in animal feeds.
Concerns and Evaluation Criteria
CVM's principal concerns over the use of garbage, waste products, by-products, or co-products are related to the poorly defined nature of the product; the numerous sources that can range from restaurants, to laundries, to industrial manufacturers; the collection vehicles/receptacles which can vary from dedicated trucks and receptacles to collection by the same trucks used to pump septic systems; the variety of contaminants possible; and the level of control (or lack of control) encompassed by local, and State laws/regulations.
In addition to the concerns stated above, the processing of potentially recyclable material can vary from minimal with no testing for contaminants to commercial processing, such as rendering, with pesticide and chemical screens. Clearly, with all these variables, regulating this portion of the recycling industry is challenging. Regulating the materials on an other than a case-by-case basis at the Federal level is currently not feasible.
Case-by-case evaluations are currently made by FDA regarding the safety of these products and their compliance with the Federal Food, Drug, and Cosmetic Act. The evaluations do not address whether the collection, disposal and processing of these products comply with State, local, or other Federal laws which might apply to waste disposal.
The safety evaluations are currently made using all available information. This information includes, but is not limited to, the source (i.e. restaurants, food processors, etc.); the contaminants present or likely to be present; the process used in processing the material for animal feed; screening procedures for detecting chemical, microbiological, and filth contaminants; collection methods/vehicles; and agreements between the supplier and processor outlining the suppliers responsibilities for preventing contamination of the recyclable material.
FDA is opposed to the use of sewer grease or any product which has come in contact with or passed through the same drain as sanitary sewer water or solid matter as a component of human or animal food. Furthermore, the Agency is also opposed to the use of grease of unknown origin as a component of human or animal food. FDA affirmed this position through regulatory action in August 1990 in which a Warning Letter was issued to a Colorado firm and again in 1994 with Warning letters to firms in Georgia and Alabama. The basis for issuance of the Warning Letters was that sewer grease or grease of unknown origin are "unfit for food" and therefore adulterated because the potential contaminants could not be known with any certainty. The FDA position specifically addresses sewer grease and grease of unknown origin and should not be interpreted as unilaterally applying to all grease trap waste.
FDA is opposed to the use of grease trap waste from floor drains, pot wash drains, dishwasher drains, sink drains, etc. in animal feed unless the contaminants were known (or not present) and did not result in unsafe tissue residues in milk, meat, and eggs or present a health hazard to animals. The Agency has not opposed the use in animal feed of "restaurant grease" or "sludge" when it consists entirely of edible by-products used in, or obtained from, the preparation of human food.
In addition to FDA guidance, the 1995 Official Publication of AAFCO includes a Note in the Fats and Oils section and definitions addressing this issue.
FDA does not object to the use of a filter cake material generated from the manufacturing of cheeses and salad dressings in animal rations for swine, beef cattle, or poultry provided it: 1) contained only food grade chemicals and/or chemicals approved for use on food contact surfaces; 2) was not collected or flocculated using polyacrylimides; 3) complies with the AAFCO definition of "Dairy Food By-Products." Furthermore, the Agency strongly recommends that the product to be recycled be collected at the cheese and salad dressing manufacturer in dumpsters designated for this use, that the dumpsters are regularly cleaned, and that the product be fed within three days of collection because of the high potential for spoilage and production of mycotoxins.
In reaching this decision, FDA used data that were submitted directly to FDA by the company and information supplied by the Illinois Environmental Protection Agency.
Garbage (dehydrated) is defined by AAFCO as a product "composed of artificially dried animal and vegetable waste (which has been) collected sufficiently often that harmful decomposition has not set in, and from which have been separated crockery, glass, metal, string, and similar materials. (Further) it must be processed at a temperature sufficient to destroy all organisms capable of producing animal diseases." If part of the grease and fat is removed, it must be designated as "Degreased Dehydrated Garbage."
In general, FDA would not object to feeding a product meeting this definition, provided it was not adulterated with a substance that would result in animal health problems or produce residues in meat, milk, or eggs (i.e., pesticides, industrial chemicals, pathogenic microorganisms, drug residues, etc.).
It is also worth noting that there are specific Federal regulations that deal with the feeding of garbage to swine. These regulations were promulgated by USDA's Animal and Plant Inspection Service (APHIS) to address the potential for the transmission of animal diseases. Feeding garbage to swine requires abiding by the regulations and obtaining a license from USDA.
These USDA/APHIS regulations state that "No person shall feed or permit the feeding of garbage to swine unless the garbage is treated to kill disease organisms . . . at a facility operated by a person holding a valid license for the treatment of garbage." These regulations also state that "Garbage shall be heated throughout at boiling (212 degrees F. or 100 degrees C. at sea level) for 30 (thirty) minutes. Garbage shall be agitated during cooking, except in steam cooking equipment, to ensure that the prescribed cooking temperature is maintained throughout the cooking container for the prescribed length of time."
An issue that has not been dealt with regard to garbage is whether it is appropriate
to include biodegradable packaging and utensils. FDA has not reviewed the safety
of this practice because, to date, no company has requested this nor have data
been submitted for evaluation. A product containing these materials may not
meet the AAFCO definition of garbage.
FDA has objected to the use of newsprint as a feed ingredient and as a bedding
material. Since bedding is often consumed by the animal, the basis for this
objection is the same for both uses. FDA initially objected to the use of newsprint
because of concerns that the process used in bleaching wood pulp could lead
to dioxin residues in the paper and that the ink may contain chemicals that
could present an animal safety problem or a residue problem in products destined
for human consumption.
Over the last several years, the process of bleaching wood pulp has changed
so that FDA's concerns for dioxin contamination are minimal. However, the problem
with inks still exists. Several newspapers have switched to vegetable-based
inks and use approved dyes for color. Until this is an industry-wide practice,
the Agency will continue to object to the general use of newsprint as a feed
ingredient or bedding material. FDA recognizes that there may be a limited number
of cases in which the particular facts and controls may enable newsprint to
be safely used. The Agency will accept proposals for these cases and provide
a case-by-case review and opinion.
In addition to the safety concerns associated with the use of newsprint as a feed ingredient, an AAFCO definition for the product would need to be established prior to its use in commercial feeds.
In April 1994, at least 4,632 cattle from 7 feedlots in Kansas became ill and 706 died. Initial investigation showed that all the feedlots had recently purchased and fed milo distillers dried grains and solubles (MDDGS) from a local ethanol production facility. An on-farm epidemiological investigation by the Kansas State Department of Agriculture, the Kansas City District Office of the FDA, and CVM showed that in addition to the MDDGS that all affected feedlots were also feeding a particular ionophore antibiotic.
The FDA investigation showed that the MDDGS was contaminated with several analogues of two macrolide antibiotics. Then, FDA conducted a detailed inspection of the local ethanol production facility which showed that this facility had processed and distilled some waste ethanol which contained two macrolide antibiotics and several analogues. This distillation took place immediately prior to the outbreak of the cattle deaths. After distillation, the solids from the waste ethanol were added to the MDDGS and caused the MDDGS to be contaminated with several analogues of two macrolide antibiotics.
Finally, a feeding trial performed by Kansas State University showed conclusively what CVM suspected following the on-farm epidemiological investigation. In the feeding trial, the macrolide antibiotic contaminated MDDGS in conjunction with FDA approved amounts of the ionophore antibiotic reproduced the clinical signs and lesions noted in the field. The FDA approved amounts of the ionophore antibiotic with uncontaminated MDDGS produced no ill effects and the macrolide antibiotic contaminated MDDGS without the ionophore antibiotic also produced no ill effects. CVM believes that the macrolide contaminated MDDGS may have potentated the toxic effects of the ionophore antibiotic.
The Center for Veterinary Medicine is concerned about both animal health and public safety. This contamination in Kansas killed feedlot cattle and also caused the potential for unsafe residues in the meat from surviving animals. The contaminated MDDGS was also sold to dairies in several states and had the potential to cause unsafe residues in the milk supply. While the FDA tested the milk from dairies exposed to the contaminated MDDGS and the USDA tested the meat from exposed animals in the feedlots to assure ourselves of a safe food supply, both agencies want to prevent the need to use limited resources to make such determinations in the future.
This example clearly illustrates our concern with the use of garbage, waste products, by-products, and co-products and the difficulty that there will be in developing universal guidance to cover the numerous products likely to be introduced on the market in the next several years.
As recycling becomes more common and non-traditional sources of ingredients enter the animal feed market, FDA wants to stress upon this segment of industry that they are producing a feed ingredient and have an obligation to produce a safe and wholesome product. Almost anything added during the process which does not become part of the primary product could become a component of animal feed. Therefore, only ingredients of the highest specifications and with a past history of safe use should be used. Industry should review all the steps involved in producing the feed by-products and, most importantly, avoid the use of ingredients or processes that might result in poisonous or deleterious substances entering animal feed.
THE REGULATORY DILEMMA OF NEWLY EMERGING DISEASES: BSE by John Honstead, D.V.M., M.S.
The following article is a discussion of bovine spongiform encephalopathy (BSE), as an example of a newly emerging disease. The article illustrates some of the difficulties and successes that regulators have in dealing with these types of diseases.An emerging disease is one that is diagnosed in a new species, where the agent has not been identified or thoroughly characterized, when the pathogenesis is poorly understood, and where the zoonotic potential is unclear. There is little published research available at the time of the emergence of the disease, and health regulators have to make decisions before further research can be completed. The dilemma for regulators is what precautions, such as regulations and requirements, should be proposed to protect human and animal health without placing unnecessary physical and economic burdens on producers, processors, and consumers. Regulators are forced to make these determinations in the absence of thorough scientific studies.
In outbreaks of emerging diseases such as canine parvo virus, AIDS, and Eboli, it has been very difficult to predict long range sequelae in order to implement protective steps in the early stages of an epidemic. In the absence of historical data on agents, diseases, and epidemics, the long-term sequelae only can be hypothesized by using other similar diseases as untested models where the predictive power of such comparisons is unknown. Emerging diseases, such as BSE, pose challenges to regulators, and require interagency cooperation.
In the beginning of an outbreak of an emerging disease such as BSE, the scientific, medical and regulatory community is at a tremendous disadvantage in determining that an unknown agent is attacking. The clinical signs may be similar to a classical disease with new features or lacking others. New species may be affected with signs of a disease seen previously in related or unrelated species. A completely new syndrome unlike any seen in the past may evolve. Often, the measurable events can only be linked epidemiologically into a description that can be used to propose control measures.
BSE is a transmissible, slowly progressive, degenerative disease of the central nervous system of adult cattle which is similar to scrapie in sheep. This disease has a prolonged incubation period in cattle following oral exposure (2-8 years) and, once symptoms appear, is invariably fatal. BSE was first recognized as a new distinct disease of cattle by researchers at the Central Veterinary Laboratory of the British Ministry of Agriculture, Fisheries, and Foods at Weybridge, England in November, 1986. However, there were indications that the first clinical case of BSE was observed as early as April, 1985.
The clinical signs of BSE involve behavioral, gait and postural abnormalities, and usually begin with apprehension, anxiety, and fear. Some cows may paw the ground or continuously lick their nostrils. There is increased reaction to sound and touch. A swaying gait, sometimes coupled with high stepping of the feet, is most evident in the hind limbs. Kicking in the parlor is also a frequently reported sign and may be accompanied by an unexpected nervousness at entrances. Changes in the normal behavior of the individual cow may be manifested as a change in the milking order, separation from the rest of the herd while at pasture, disorientation, staring at imaginary objects, and excessive licking of the nose or flanks.
There are few if any gross pathological changes evident at necropsy other than loss of body condition in some animals. However, post mortem histopathology of BSE closely resembles other transmissible spongiform encephalopathies (TSE's). Histopathological examination also demonstrates bilaterally symmetrical degenerative changes in gray matter neuropil and neuronal vacuolation. Because of their structure and methods of replication, the BSE agents do not provoke an antibody response in the host, removing the possibility of detecting their presence by serological techniques or of preparing protective vaccines.
BSE Epidemic in the United Kingdom (UK)
Since BSE was first diagnosed in the United Kingdom in December 1986, more then 155,000 cattle have contracted the disease. BSE has now been reported in France, Switzerland, Oman, Portugal, the Republic of Ireland, and Northern Ireland.
Epidemiological studies in the UK have characterized the outbreak of BSE in
that country as an extended common source epidemic. Each case, therefore, has
been a primary case due to exposure to a single common source of infection.
Investigators have identified several major risk factors that apparently contributed
to the emergence of the disease and the resultant epidemic in the UK. USDA identified
the following risk factors for BSE in the UK:
In the UK, dead sheep, many of which may have died of scrapie and cattle with BSE, were picked up by "knackers" for rendering into animal feed. This material was partially rendered into "greaves" which contained large amounts of the scrapie/BSE agent, and was fed to dairy calves in large amounts. The spread of BSE appeared to be facilitated by the feeding of rendered BSE-infected cattle back to calves. BSE agent recycled from cows to calves until the ruminant-to-ruminant feeding ban in 1989.
Efforts to Control BSE in the UK
In the late 1970s and early 1980s, many rendering plants in Britain switched from the hydrocarbon extraction solvent rendering method using live steam to a heat extraction method. The heat extraction method apparently allowed the survival of BSE present in UK cattle.
In an extensive research project, various rendering processes used in the European Union were tested for their ability to inactivate the BSE agent in 15 pilot scale facsimiles. BSE brains were mixed with intestine and bone to replicate raw materials. The variables were type of process (continuous or batch), time, temperature, atmosphere, amount of fat, and particle diameter. Meat and bone meal was produced from each of the processes, and suspensions were assayed in inbred mice for infectivity. Four of the 15 processes produced meat and bone meal with detectable BSE infectivity, and one process showed no reduction in titer over the original raw material. These processes were banned for use in the EC.
Regulatory controls taken to manage the BSE epidemic and minimize public health risks in the UK and other countries include an action to make the disease reportable (June, 1988); a ban on the feeding of ruminant-derived protein supplements to other ruminants (July, 1988); compulsory slaughter and incineration of suspect cattle (August, 1988); and a ban on the feeding of the specified offals or their products to all pet and farm animals (September, 1990). There is no direct evidence that scrapie or BSE is a hazard to human health. Nevertheless, British authorities have banned from human foods and all animal feeds the use of specified bovine organs (brain, spinal cord, thymus, tonsils, spleen, and intestines), from cattle over 6 months of age and products derived from them.
Efforts to Prevent BSE in the U.S.
The first step in dealing with an emerging animal disease, such as BSE, is identifying and measuring the risks to U.S. livestock posed by other countries with the disease, and understanding conditions in the U.S. which might lead to an outbreak.
To date, no cases of BSE have been diagnosed in the U.S. If a BSE outbreak occurred in the U.S., there would be a significant animal health risk and a perceived human risk. The animal health risk would be from ruminants consuming rendered infected cattle. The perceived human risk would come from fears that humans could be at risk for Creutzfeldt-Jacob Disease (CJD) from consuming foods, dietary supplements, or drugs derived from bovine tissues. Also, it would likely have a devastating economic effect on the U.S. cattle industry. Not only would the sale of beef in the U.S. likely plummet, as it did in Britain, but domestic use and exports of cattle by-products would likely be restricted until the U.S. could demonstrate the disease was eradicated or under control. Since BSE has a mean 3.5 year incubation period, it would take a long time to demonstrate safety of U.S. cattle by-products following the diagnosis of the first case.
The reduction in the titer of TSE agents by the processes used by renderers in the U.S. is one of the important conditions in the U.S. that is protective against a UK-type epidemic. Renderers in the U.S. did not manufacture greaves as in the in the UK. The small sheep population, small amount of scrapie, large cattle population, lack of feeding meat and bone meal to young bovines, young age of U.S. dairy cattle, in addition to the rendering conditions are reducing the risk of BSE in U.S. indigenous bovines.
USDA's Animal and Plant Health Inspection Service (APHIS) regulations for Foreign Animal Diseases along with many special regulations for BSE have helped prevent importation of BSE animals into the U.S. APHIS has also carried out an effective surveillance program for BSE in U.S. cattle and performed several thorough risk assessments for BSE in the U.S. to monitor the change in risk for U.S. cattle. APHIS has prohibited the importation of live cattle and zoo ruminants from Great Britain since July, 1989. Pathologists at the National Veterinary Service Laboratories (NVSL) and the Iowa State University are examining bovine brains submitted. NVSL personnel have examined over 2,000 bovine brains and none of these specimens contained lesions with the characteristics and distribution typical for BSE.
In 1989, the National Renderers Association and the Animal Protein Producers Industry recommended to their members that they voluntarily refrain from rendering sheep offal for inclusion in cattle feed.
BSE was still an emerging disease in 1992, and as discussed, little factual information was known except that feed ingredients from UK rendering were transmitting BSE and it was similar to scrapie. Therefore, in 1992, the Food and Drug Administration (FDA) carried out a survey of current rendering practices in the U.S. The survey showed that the rendering industry voluntary ban was not adequately effective. The survey showed some rendered adult sheep protein getting into U.S. cattle feed. Limited inspections of rendering plants were conducted to:
In 1993, FDA determined that the most prudent course of action was to develop means to further reduce the risk to U.S. cattle. The FDA issued letters to manufacturers of drugs, biologics, devices, dietary supplements, and animal products urging them to use only cattle products from non-BSE countries in their products. A regulation was proposed to protect cattle from the possibility that scrapie had caused BSE. The major benefits of the regulation were:
BSE is an example of an emerging disease with considerable impact on USDA, FDA, and the world. Regulators have an especially difficult task in protecting human and animal health in the face of inadequate scientific information. The successful solution to the UK BSE epidemic and no evidence of BSE's presence in the U.S. is testimony to the advantages of government Agency communication and cooperation in the face of a devastating emerging disease.
The following firms/individuals received warning letters for offering animals for slaughter that contained illegal drug residues:
These violations involved illegal residues of neomycin in calves, penicillin in cows, oxytetracycline in a cow, gentomycin in a calf, and chlortetracycline in a cow.
M&S Feeds, Inc., Madelia, MN, received a warning letter for deviations from the Good Manufacturing Practice (GMP) regulations.
In the February 21, 1996 Federal Register, FDA announced the availability of a guidance document entitled "Guidance on Generic Animal Drug Products Containing Fermentation-Derived Drug Substances." The guidance is intended to provide sponsors with information that will enable them to submit complete and well-organized chemistry and manufacturing and control information for generic animal drug products containing fermentation-derived drug substances.
Copies of the document are available from the FDA Veterinarian. Please send two self-addressed adhesive labels to assist in processing your request. Further information on this document is available from Dr. David R. Newkirk, Center for Veterinary Medicine (HFV-142), FDA, 7500 Standish Place, Rockville, MD 20855.
Written comments on the guidance document 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.
FDA ANALYZES PESTICIDES IN ANIMAL FEEDS
In Fiscal Year 1995, 556 domestic feed samples (532 surveillance and 24 compliance) and 69 import feed samples (65 surveillance and 4 compliance) were collected and analyzed for pesticides by the FDA. Of the 532 domestic surveillance samples, 301 (56.6 percent) contained no detectable pesticide residues and only 2 (0.4 percent) contained residues which exceeded regulatory guidance (see Table I). Of the 65 import surveillance samples, 29 (44.6 percent) contained no detectable pesticide residues, and only 1 (1.5 percent) contained residues which exceeded regulatory guidance.
Two domestic samples of corn (1 each from Virginia and Missouri) contained .034 and .304 parts per million (ppm) of chlorpyrifos-methyl. One import sample of feather meal from Canada contained .060 ppm of diphenylamine. Since there is no tolerance established for chlorpyrifos-methyl on corn or for diphenylamine on poultry, these samples were considered to have exceeded regulatory guidance.
In the 231 domestic surveillance feed samples in which one or more pesticides
were detected, there were 346 residues (254 quantifiable and 92 trace). Malathion,
chlorpyrifos-methyl, diazinon, chlorpyrifos, and pirimiphos-methyl were the
most frequently found pesticides and accounted for 90.75 percent of all residues
detected in feed (see Table II).
TABLE I - Summary of the 532 domestic feed samples that were collected and analyzed for pesticide surveillance by the FDA in Fiscal Year 1995.
| TYPE OF FEED |
# of Samples |
Samples With No Pesticide Residues |
Samples Exceeding Regulatory Guidance |
| Whole/Ground Grains | 167 | 98 (58.7%) | 2 (1.2%) |
| Plant By-products | 120 | 76 (63.3%) | 0 (0.0%) |
| Mixed Feed Rations | 116 | 35 (30.2%) | 0 (0.0%) |
| Animal By-products | 104 | 74 (71.2%) | 0 (0.0%) |
| Hay & Hay Products | 25 | 18 (72.0%) | 0 (0.0%) |
| TOTALS | 532 | 301 (56.6%) | 2 (0.4%) |
TABLE II - Summary of the pesticides in the 231 domestic feed samples that contained one or more detectable residues. These samples were collected and analyzed for pesticide surveillance by FDA in Fiscal Year 1995.
| Number of Samples with Pesticide | Trace Amounts** | Quantifiable Levels | Range* (ppm) | Median* (ppm) |
| malathion | 33 | 149 | 009 - 7.680 | .086 |
| chlorpyrifos-methyl | 21 | 39 | .010 - 1.100 | .108 |
| diazinon | 9 | 23 | .011 - .812 | .060 |
| chlorpyrifos | 16 | 10 | .006 - .082 | .030 |
| pirimiphos-methyl | 5 | 9 | .011 - 9.850 | .050 |
| all others | 8 | 24 | .008 - 40.700 | .190 |
** the residue found is below that normally quantifiable, but its presence and identity are known. * in samples containing quantifiable levels.
DIPHENYLHYDANTOIN SODIUM CAPSULES, Parke-Davis, Division of Warner-Lambert Co., (NADA 6-032). The firm requested withdrawal because the product is no longer being marketed. Effective date: December 22, 1995.
STERILE PREDNISOLONE SUSPENSION, PHENYLBUTAZONE INJECTION, AND DEXAMETHASONE INJECTION, Akorn, Inc., (NADAs 12-444, 94-978, and 110-046). The firm requested withdrawal because the products are no longer being marketed. Effective date: December 22, 1995.
COPPER DISODIUM EDETATE INJECTION, Veterinary Research and Development, Inc., (NADA 140-904). The firm requested withdrawal because the product is no longer being marketed. Effective date: December 22, 1995.
FOOD SAFETY EVALUATION OF TRANSGENIC ANIMALS by Margaret Ann Miller, Ph.D. and John C. Matheson III, MSPH
Recombinant DNA (rDNA) and related genetic modification techniques are being applied to food-producing animals. These modifications are being performed for a variety of reasons such as to produce biologics and pharmaceuticals, optimize the nutritional value of derived food products, improve animal growth rate and reproduction, prevent animal disease, select superior strains, identify individuals, and preserve genetic stocks. Many of these applications fall outside the purview of the Federal Food Drug and Cosmetic (FFD&C) Act which is enforced by FDA. In other cases, the product claims for the genetic modification and the animals containing them are very similar to those of products currently regulated by FDA. While the Agency has not published a formal policy on the regulation of these "transgenic" animals, some of these techniques and product claims may come under the FFD&C Act.
Products regulated as new animal drugs in the United States are subject to a pre-market review process to determine efficacy and safety. Product safety includes target animal safety, safety to the environment, and safety for consumers of food derived from treated animals. The new animal drug approval process permits experimental animals to enter the food supply after the FDA determines that the food products are safe for human consumption. Although it is difficult to predict for future products, the current regulations can accommodate the present generation of genetically modified animals for which food safety may be of concern.
During the past few years, the FDA has published several policy statements and guidelines discussing the Agency's position on the regulation of products produced by biotechnology. For example, in May 1992, FDA published a document in the Federal Register entitled "Statement of Policy: Foods Derived from New Plant Varieties." This document outlines the decision-making process and safety assessment that food producers should follow prior to marketing "transgenic" plants as human food and animal feed. Also, in 1995, FDA's Center for Biologics Evaluation and Research published a guidance document "Points to Consider in the Manufacture and Testing of Therapeutic Products for Human Use Derived from Transgenic Animals." This document discusses guidance for the manufacture of pharmaceuticals by "Biopharm" animals as well as a recommendation that the FDA determine food safety before these animals enter the human food supply.
Other Federal agencies also regulate genetically modified animals. USDA has authority to regulate viruses under the Virus, Serum, and Toxin Act. Therefore, when viral vectors are used to introduce the new genetic material into animals, the viral component of the gene construct may be under the jurisdiction of USDA's Animal and Plant Health Inspection Service.
USDA's Food Safety and Inspection Service (FSIS) is responsible for ensuring the safety, wholesomeness and accurate labeling of all meat, meat food products and poultry products under the Federal Meat Inspection Act and Poultry Products Inspection Act. FSIS has developed a Points to Consider document "Safety Evaluation of Transgenic Animals from Transgenic Animal Research."
EPA regulates all pesticides under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) and controls the use of genetically engineered microorganisms (GEMs) under the Toxic Substances Control Act (TSCA). EPA is not principally involved in regulating transgenic animals.
FDA is the primary agency responsible for the regulation of food products intended for human consumption. FDA has responsibility for the safety of milk and dairy products, fish and shellfish, and animal drug products. To date, FDA has not published a formal policy statement on how the FFD&C Act applies to the regulation of new gene transfer technologies when used in food-producing animals. In transgenic animal experiments, the new genetic material may be introduced into either the germ line or all or some somatic cells. In many cases, the expression product and the product claims for the transgene are identical or very similar to products which are currently regulated by the Agency as animal drugs.
The FFD&C Act defines drugs based upon their functional claims rather than their chemical structure or manufacturing source. Some transgenic animals will be regulated under the animal drug provisions of the FFD&C Act. When the genetic material is introduced into somatic or germ cells to produce a phenotypic change in the animal or its offspring, it would be considered to be an animal drug. On the other hand, when a genetic procedure is used to map the genome and phenotypic change is achieved through selection and traditional breeding, it would not be considered to be involving the use of an animal drug.
The animal drug approval process is primarily designed for drug sponsors seeking FDA approval to market drugs in interstate commerce. However, this process is also used to facilitate research on food-producing animals so that the experimental animals can enter the food supply. Researchers conducting experiments with animal drugs in food-producing animals can establish an Investigational New Animal Drug Application (INAD) with the CVM.
Under the INAD process, researchers have an opportunity to conduct all the studies required to support the commercial marketing approval. Once the sponsor demonstrates the safety of food products from the treated animals, the experimental animals can enter the food supply.
Human Food Safety Requirements For Animal Drugs
While FDA's Center for Food Safety and Applied Nutrition (CFSAN) regulates the vast majority of food for humans, i.e., food commodities consumed directly by humans, the Center for Veterinary Medicine (CVM) ensures the safety of animal drug residues which are regulated as indirect food additives. The safety determination for animal drug residues in food for humans ("human food safety") is not dictated by the drug claims but by the chemical nature and biological activity of the drug entity. The human food safety concern for animal drug residues focuses on the assessment of chronic low level exposure effects of drug residues in edible tissues. Generally, the concentration of drug residues in edible tissues are not high enough to produce acute toxicity.
For most animal drugs, the human food safety evaluation involves the completion of the standard battery of toxicology tests and residue and metabolism studies. These toxicology tests are designed to determine the dose at which the compound produces an adverse effect in test animals and a dose at which the drug produces no adverse effect, i.e., the no observed effect level (NOEL). The observed effect does not always represent a toxic effect. Pharmacological, hormonal, and microbiological effects are all considered adverse biological effects in the human food safety evaluation. For certain drug classes, additional specialized tests are required to establish a NOEL for these physiological effects.
In addition to the general food safety provisions of the FFD&C Act, the Delaney Clause prohibits the use of carcinogenic compounds as animal drugs when they leave residues in food. Therefore, if the animal drug or its metabolites are structurally related to a demonstrated carcinogen or if the compound tests positive in the genetic toxicology studies, additional carcinogenicity studies may be required.
Following completion of all the toxicology studies, the NOEL of the most sensitive effect from the most appropriate toxicology study is divided by a safety factor to determine an acceptable daily intake (ADI). The ADI represents the highest amount of total residue of the compound that is allowed in edible tissues of the target animal. This total residue consists of parent compound, free metabolites, and metabolites that are covalently bound to endogenous molecules, and is very difficult to measure on a routine basis. Rather than measuring the total residues in all the edible tissues, CVM establishes one value, a tolerance, in one tissue, the target tissue for monitoring drug residues. The tolerance is established so that when residues are below the tolerance in the target tissue, the whole carcass is safe. To establish the tolerance for the drug, the drug sponsor conducts a residue depletion study to determine when the concentration of total drug residues is below the ADI.
This food safety assessment process using a toxicology test battery works very well for drugs that have toxicology endpoints which display a clearly observable dose-response relationship. This approach is not appropriate for determining the food safety of all animal drugs and certainly must be modified for assessment of transgenic animals.
The FFD&C Act also requires a determination of the safety of compounds formed in food as a result of drug treatment. For "traditional" animal drug products this provision serves as a basis for an examination of metabolites. For the recombinant protein products, CVM has interpreted this provision to require examination of the food safety implications of secondary metabolic changes which occur as a result of drug treatment. For genetically modified animals this provision could require an assessment of pleiotrophic changes.
Recombinant Animal Drug Products
To date, the biotechnology products approved by CVM have been proteins produced by recombinant DNA technology using a bacterial fermentation system. The desired gene is isolated and fused with plasmid DNA. The recombinant plasmid is cloned or inserted into a gram negative bacterial host, usually Escherichia coli. Under fermentation conditions, these transformed microorganisms become factories which produce large quantities of the protein hormone product at relatively low cost. The protein product is isolated and purified from the bacteria. When treated under defined conditions, the product assumes a conformation which is biologically active. In many respects the production of recombinant protein hormones is not substantially different from the production of other new animal drugs made by fermentation processes.
The food safety evaluation for recombinant protein hormone products is similar to that performed for other protein products approved as animal drugs. On the other hand, the toxicology studies conducted to demonstrate the human food safety of protein products are considerably different from those just described for more traditional animal drug products.
For protein hormones that are biologically active in humans and for recombinant proteins with altered amino acid sequences, the human food safety assessment compares the oral bioavailability of the protein to the concentration of the protein residues in tissues. For compounds with extremely low oral bioavailability, it is possible for humans to consume the entire dose administered to the food animal with no food safety concerns. In other cases, the sponsor must quantify the protein hormone concentration in edible tissue to assure an adequate margin of safety between the oral dose where no bioavailability is demonstrated and the levels expected to be consumed by humans as residues.
Food Safety Determination of Transgenic Animals
Transgenic Animals Containing an Animal Drug
The statutory food safety requirements for animal drug residues resulting from genetic modification of animals are the same as those for other animal drugs. Basically, the food products produced from genetically modified animals must be as safe as those from nontransgenic animals, and the sponsor of the transgenic animals must demonstrate safety of the animal products before the animals can enter the food supply. The standard battery of toxicology studies used to establish the safety of "traditional" animal drugs are not appropriate for assessing the safety of transgenes in genetically modified animals. Also, the "traditional" withdrawal period may be difficult to apply to transgenic animals. It may not always be possible to "turn-off" the expression of the transgene, and thereby limit exposure to the expression product to a tolerance concentration. Also, the transgene will still be present in the animal. In cases where there are food safety concerns for the expression products and not the transgene, a tolerance approach could apply.
CVM does not plan to offer a standard set of guidelines on how the food safety determination for transgenic animals must be conducted. Sponsors seeking approvals for transgenic animals with animal drug claims are, instead, encouraged to contact the CVM early in the development process so that a case-specific human food safety program can be designed.
Many different transgenic animal products could potentially be offered to the market for food, yet few living examples are available for evaluation. Ultimately, transgenic animals modified specifically to improve the economics of producing them for food or to improve other desirable characteristics, such as lean-to-fat ratios, are expected to be a common situation. Gene therapy may be used to combat disease in specific tissues, such as treatment of mastitis, or to create secondary sites for the release of growth hormones or other production enhancement gene products. Stable germ lines containing genetic modifications that relate to productivity or disease resistance are also likely, particularly in fish.
Generally, the human food safety assessment for transgenic animals will be more similar to that performed on recombinant protein products than that performed on the "traditional" drugs. The product's sponsor will need to demonstrate the safety of: 1) the transgene, including the promoter and other unexpressed regions; 2) the expression products and 3) in some cases, pleiotrophic effects, in edible animal products. Information on the biology of the genetic modification from the scientific literature, data on the biochemical characterization of the transgene and the expression products, information on the mode of action, data on the quantity of transgenes and expression products, and studies investigating oral bioavailability of the expressed protein will be useful in performing the food safety assessment.
Biopharm animals have been genetically modified to manufacture a human or veterinary drug or biologic substance, a food additive, or other product of commercial value. The substance is then harvested from milk, blood or other tissue of the animal. The genetic modification can be either a germ line (heritable) modification, or a somatic cell/gene therapy involving the introduction of the modified genes into cells of a particular organ or tissue of an individual. The main emphasis of these efforts is on harnessing the metabolic capabilities of the animal to produce a product in lieu of using, for example, chemical synthesis, fermentation, or extraction from a dilute natural source.
Biopharm animals are usually of the same species that humans use for food, so it can be anticipated that sometimes it will be desired to salvage them for food, thereby avoiding other more costly means of carcass disposition. Safety evaluation of food derived from biopharm animals would include, in addition to the factors addressed above, an evaluation of effect of the management of the animals on their residue profile. Animal management would be examined for the potential for unsafe residues of drugs and other chemicals that were used during the utilization of the animal as a protein factory.
Not surprisingly, biopharm animals are sometimes managed with research compounds, unapproved and approved drugs and biologics in order to facilitate production of biopharm products. Because of later purification steps, these research compounds do not appear as residues in the biopharm product, however the residues may remain in portions of the animal that might be offered for food. If the safety of these residues in animal tissues cannot be demonstrated, the animals cannot be offered for food.
Transgenic Animals Containing Food Additives and Color Additives
A third grouping of transgenic animals are those modified in a manner to affect their quality as food for humans. Examples might include cattle producing more nutritionally complete milk, fish that produce more omega-3 fatty acids, and farm-raised trout whose flesh is pinker. It is anticipated that CFSAN, rather than CVM, will evaluate these types of modifications under the food additive, color additive or Generally Recognized As Safe (GRAS) provisions of the FFD&C Act.
Many of the product claims being anticipated for transgenic animals, such as improved growth, improved feed efficacy, improved carcass characteristics, and improved disease resistance, are the same as animal drug claims. Any regulation of transgenic animals under the FFD&C Act will require a demonstration of human food safety before the animals enter the human food supply.
This issue of the FDA Veterinarian contains the third in a series of questions and answers that are frequently asked about CVM's Veterinary Adverse Drug Experience (ADE) program.
Q. If I decide to report an ADE, who should I contact?
A. You should first call the drug company. Inform them that you wish to report an ADE, and ask to speak to a technical services veterinarian. The technical services veterinarian should ask a series of questions about the experience, complete a form called the FDA 1932, and forward the report to CVM. We suggest the drug company as your first point of contact because many companies also will offer clinical advice or diagnostic assistance. CVM does not provide these services. Drug company telephone numbers can be obtained from the publications Compendium of Veterinary Products (North American Compendiums, Inc.) and Veterinary Pharmaceuticals and Biologics (Veterinary Medicine Publishing Company).
If you wish to confirm that your report was forwarded, or prefer not to call the drug company, you can contact CVM directly at (301) 594-1722 or toll-free at (800) FDA-1088. Please ask to speak to one of the veterinarians responsible for the ADE monitoring program. CVM can also provide a supply of prepaid mailers (Form FDA 1932a). These mailers are available by writing or telephoning CVM and are also distributed at veterinary medicine meetings and seminars.
If the ADE involves a product other than a drug, the following numbers may be useful. The telephone number to reach USDA regarding biologics is (800) 752-6255. The phone number to reach EPA regarding topical insecticides is (800) 858-7378.
A third option for reporting is the Veterinary Practitioners' Reporting Network (USP PRN) sponsored by the United States Pharmacopeia (USP). The USP PRN program is an independent, non-government reporting program. The telephone number to reach USP regarding any veterinary product is (800) 4-USP PRN.
Q. Does CVM review reports that involve extra-label use of animal drugs?
A. The reporting of ADEs associated with extra-label use is important
to the veterinary profession. Under the Medicinal Drug Use Clarification Act
of 1994, veterinarians can, in the future, administer drugs more freely in an
extra-label manner. About one third of the current ADE reports on file involve
extra-label use. CVM is also interested in ADEs involving human drugs used in
veterinary practice, and in ADEs involving animal drugs marketed without FDA
approval.
MICROBIOLOGICAL TESTING GUIDANCE AVAILABLE
In the January 30, 1996 Federal Register, FDA announced the availability of a guidance document entitled "Microbiological Testing of Antimicrobial Drug Residues in Food." This guidance document addresses human food safety issues that may be associated with food-animal antimicrobial drug products. This publication also provides points to consider when determining which antimicrobials may require supplemental testing, and recommends test procedures for establishing that antimicrobial drug residues will not cause intestinal microflora perturbations in the consumer. Written comments on the guidance document 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. Copies of the document are available from the FDA Veterinarian. Please send two self-addressed adhesive labels to assist in processing your request. Further information on this document is available from Dr. Haydee Fernandez, Center for Veterinary Medicine (HFV-154), FDA, 7500 Standish Place, Rockville, MD 20855.
FOOD ADDITIVE REGULATIONS AMENDED
In the January 2, 1996, Federal Register, the FDA announced that the Agency is amending the food additive regulations to provide for the safe use of menadione nicotinamide bisulfite as a nutritional supplement for the prevention of vitamin K deficiency and as a source of supplemental niacin in chicken and turkey feed when used at a rate not to exceed 2 grams per ton (g/t) of complete feed. This action is in response to a food additive petition filed by Vanetta (U.S.A.), Inc.
INFORMATION ON MARKETING A PET FOOD PRODUCT
The following article is provided in response to numerous inquiries CVM
has received concerning pet food regulations.
There is no requirement that pet food products have premarket approval by FDA. The Federal Food, Drug, and Cosmetic Act does require that pet foods, like human foods, be pure and wholesome, contain no harmful or deleterious substances, and be truthfully labeled. Canned pet foods must be processed in conformance with low acid canned food (LACF) regulations designed to ensure that the finished product is free of any viable microorganisms. Producers must file acceptable processing methods with the Agency. These LACF regulations [listed in Title 21 of the Code of Federal Regulations (CFR), Part 507] are equivalent to the LACF requirements for canned foods intended for human use .
The Federal Food, Drug, and Cosmetic Act states that foods intended for man or animals are adulterated if they contain color additives that have not been proven safe to the satisfaction of FDA for that particular use. Title 21 of the CFR, Parts 73, 74, and 81 list the approved color additives and the conditions under which they may be safely used in food, including the amounts that may be used.
Regulations which apply specifically to food additives in animal pet foods are published in Title 21, Part 573 of the CFR. Additives in pet food must be approved by FDA based on scientific evidence that supports their safety and utility. If FDA has reason to believe there is a problem with the safety of a particular food additive, the Agency can take action to have it removed from the market.
There are also Generally Recognized as Safe (GRAS) substances which are permitted to be used in pet foods, because of their long history of safe use in foods. These are published in Title 21, Part 582 of the CFR.
Regulations concerning the labeling of pet food are published in Title 21, Part 501 of the CFR. Copies of the CFR may be purchased from the Superintendent of Documents, Government Printing Office, Washington, DC 20402.
Pet food labeling is regulated at two levels. The Federal regulations, enforced by FDA, establish standards for all animal feeds: proper identification of the product as a pet food; net quantity statement (weight, volume, or count); name and place of business of the manufacturer, packer, or distributor; and proper listing of all ingredients in descending order of predominance by weight and identified by their common or usual names. Some States also enforce their own labeling regulations. Many of these follow the pet food regulations of the Association of American Feed Control Officials (AAFCO), a nongovernment advisory body with representatives from all States.
The Association of American Feed Control Officials has issued a series of pet food regulations that has served as a model for State laws and regulations. These include more specific requirements regarding product names, flavor designations, guaranteed analysis, nutritional adequacy statements, proper ingredient names, and other aspects of labeling. The organization also provides test requirements or protocols for manufacturers so that they can meet State requirements of proof of safety and nutritional quality before a pet food is marketed. A product clearly identified as a "snack" or "treat" does not require a nutritional adequacy statement, but it must meet the other pet food regulations.
To order a copy of its official publication, you may write to:
Charles Frank, Treasurer
Association of American Feed Control Officials
Georgia Department of Agriculture
Plant Food, Feed and Grain Division
Capitol Square
Atlanta, Georgia 30334
(404) 656-3637
Although not explicitly addressed in FDA or AAFCO regulations, there are also policies or procedures regarding other aspects of labeling, such as health claims, use of the term "natural," etc. For further information or clarification of these issues or FDA pet food regulations, you may contact:
Center for Veterinary Medicine
Division of Animal Feeds (HFV-220)
Office of Surveillance and Compliance
7500 Standish Place
Rockville, Maryland 20855
(301) 594-1724
In the February 6, 1996, Federal Register, FDA announced the availability of target animal safety and effectiveness data and human food safety data to be used in support of a new animal drug application (NADA) or supplemental NADA for use of 1 percent ivermectin injection in American buffalo. The data, contained in Public Master File (PMF) 5059, were compiled under National Research Project No. 7 (NRSP-7), a national agricultural program for obtaining clearances for use of new drugs in minor animal species or in any animal species for the control of a disease that occurs infrequently or in limited geographical areas. Further information is available from Dr. Jean M. Cooper, Center for Veterinary Medicine (HFV-130), Food and Drug Administration, 7500 Standish Place, Rockville, MD 20855.
Continue to NEW ANIMAL DRUG APPROVALS CHART AND REVISED ANIMAL DRUG APPROVALS