The national milk safety program and drug residues in milk.

There are a number of factors that must be considered in any attempt to control animal drug residues in milk and milk products. Dairy herds vary greatly in number of cows. Milk from individual cows and farms is pooled, diluting drug residues that may be present in the milk from a single treated cow. Management techniques, including the handling, administration, and record keeping of animal drugs, vary greatly from one dairy to another. It is important that both veterinarians and nonveterinarians adhere to adequate milk discard times for animal drugs used to treat dairy animals. Observance of appropriate safeguards at the farm level, such as record keeping and clearly identifying treated animals, is critical for controlling and preventing the presence of illegal animal drug residues. Within the framework of the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act, the FDA is working with state and other regulatory agencies and industry to better ensure the absence of illegal animal drug residues in milk and milk products. Preventive measures concentrate on minimizing the need to administer animal drugs to lactating cows, and diverting milk containing drug residues from the human food supply. Monitoring programs concentrate on screening milk and tracing violations to the individual producer. Minimizing illegal drug residues in milk and milk products requires close cooperation between farmers, veterinarians, the dairy industry, the pharmaceutical industry, and regulators.     

Legal implications of the extra-label use of drugs in food animals

Although the Food and Drug Administration has never sanctioned the extra-label use of drugs in animals, it has not, until recently, objected when veterinarians deviated from label instructions as long as such use did not result in violative residues in food products derived from treated animals. However, because of the potential human health hazards associated with abuse of this position, the FDA has developed a less lenient policy toward the extra-label use of drugs in food animals. A brief review of the legislated responsibility and authority of the FDA with particular reference to the extra-label use of drugs in food animals is provided. Emphasis is placed on how anesthetics and anesthesia adjuncts in food animals can pose human health hazards.     

Dispensing law and sale of animal feed

For the veterinarian, drug sale is generally permitted by his licence of drug dispensing. According to the law on animal feed, feedstuffs are not regarded as drugs and thus they are not licensed to be sold by veterinarians. Drugs, however, may only be released for the treatment of individual animals, which are previously examined by the vet. The sale of animal feed is not regarded as part of veterinary practice. Only in case of a registered additional business, a veterinarian is allowed to sale feedstuffs. Dietetic animal feedstuffs are also regulated by the Animal Feed Act. Dietetic drugs, however, are regulated by the Drug Act and are strongly to be delineated from dietetic feed. Thus, the term "dietetic" alone does not automatically give any legitimatization for a sale of feedstuffs in veterinary practice.     

Developing new regulatory approaches to antimicrobial safety

Resistance to antimicrobial agents is of concern to public health officials worldwide. In industrialized countries, a significant source of antimicrobial-resistant food-borne infections in humans is the acquisition of resistant bacteria originating from animals. The US Food and Drug Administration (FDA) is committed to resolving the public health impact arising from the use of antimicrobial drugs in food-producing animals. The FDAs goal is to ensure that significant human antimicrobial therapies are not compromised or lost while providing for the safe use of antimicrobials in food animals. Recently the FDA published a guidance document titled 'Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to their Microbiological Effects on Bacteria of Human Health Concern' (US Food and Drug Administration, Center for Veterinary Medicine, 2003). This document outlines a pathway drug sponsors can use to address concerns about antimicrobial resistance prior to approval of their drug. The process uses a qualitative risk assessment approach to assess the potential of the intended use of a product to develop resistance in bacteria that may harm humans. The level of risk determines the level of risk management that is required for the drug to be used. The Food and Drug Administration (FDA) always has the option of not approving a drug if the risk of a public health consequence is too high.     

Drug residues in food animals

A total of 292 field investigative reports of drug residues in food animals for 1983 to 1988 were analyzed. The investigations had been conducted by the Food and Drug Administration (FDA) and the Virginia State Veterinarian's Office, in cooperation with the Center for Veterinary Medicine of the FDA, to trace residues reported by the USDA Food Safety and Inspection Service to the source of the animal and the administration of the drug. The analysis disclosed the following. (1) Antibiotic residues were most often associated with streptomycin, penicillin, oxytetracycline, and neomycin. Sulfamethazine was, by far, the most frequently cited sulfonamide. (2) Residues are being found predominantly in cows, veal calves, and market hogs (barrows and gilts). (3) The cause of drug residue most frequently cited by the field investigators was failure to observe the withholding time for the drug. Almost half of these investigations revealed that the individual responsible for the sale of the animal did not know the proper withholding time for the drug. Failure to maintain adequate records was also a contributing factor. (4) The producer was considered to be the responsible party in over 80% of the cases for which responsibility was determined. (5) Residues associated with injectable drugs were investigated most frequently. Long-acting and sustained-release products were most often associated with penicillin and oxytetracycline residues. (6) The 2 most common sources of purchase for the drugs involved in the investigations were the feed/farm supply store and the veterinarian. (7) Unapproved drug use was not a major cause of residues.     

"抗菌新兽药对与人类健康相关细菌微生物学影响的安全性评价"指导原则简介

在食品动物使用抗菌药,可能导致耐药菌产生,耐药菌在人畜间的传递导致产生交叉耐药性.FDA对此制定了安全性评价指导原则.本文简要介绍了抗菌新兽药对与人类健康相关细菌微生物学影响的安全性评价指导原则.该指导原则主要内容包括:释放评价、暴露评价、后果评价、危险评估及危险管理措施制定等.毫无疑问,这一指导原则对我国抗菌新兽药管理和食品安全管理会有所启迪.     

Basis for regulation of selenium supplements in animal diets.

Selenium was discovered 174 yr ago but, until 1957, was given little notice by biologists or was vilified as an agent that caused toxicity in grazing ruminants and horses in the northern Great Plains. After its status as an essential nutrient was established, Se received intense scrutiny, and hundreds of papers have been published dealing with its metabolic functions and the consequences of a Se deficiency. Because regions of Se deficiency are so extensive in the United States, great efforts have been made to gain Food and Drug Administration (FDA) approval for Se supplementation of animal diets. Initially, these efforts were thwarted by concern that Se might be carcinogenic. After this concern was resolved, researchers established supplemental Se levels that were efficacious, safe for animals, safe for humans that eat animal products, and protective of the environment. First approval of Se supplements was given in 1974 for supplementation of swine or growing chicken diets at .1 ppm. Supplements for turkey diets were approved at .2 ppm. Ultimately, in 1987, levels of supplemental Se in diets for chickens, turkeys, ducks, swine, sheep, and cattle were approved at .3 ppm. However, FDA regulations do not mention horses or zoo animals, and those who would ensure the welfare of these species by supplementing Se-deficient diets may be in violation of FDA interpretation of the law. In addition, the association of Se with death and deformities in aquatic birds at the Kesterson Reservoir in California has led to pressure on the FDA to reverse the 1987 amendments to the feed additive regulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

FDA fast-tracking of pet population control drugs

Theriogenologists have been studying estrus prevention and termination of pregnancy in dogs for at least 2 decades. However, drugs approved for estrus suppression are few. No dog or cat abortifacients or male dog and cat sterilants have been approved. Marketed drugs with alternate indications that have antiestrus and antihormonal activity might be good candidates for study after obtaining an INAD from FDA. With the support of the original drug sponsor or manufacturer and appropriate safety and effectiveness studies, these products may be studied for additional label claims. New (not previously approved) drugs additionally need detailed information regarding the synthesis and manufacturing controls. Drugs offering substantial benefit over existing therapeutics may be eligible for expedited review. Prior to starting any studies in this area, clinical investigators and sponsors should communicate with FDA, an INAD must be granted, and the protocol submitted for evaluation. Approvability is evaluated after establishment of safety and effectiveness in clinical field trials.     

Veterinary drug legal situation for oral medication in animal facilities in Germany

Oral medication of animal stocks can be administered via oral ready-to-use veterinary medicinal products or by using medicated feedingstuffs. The regulations contained in the German Drug Act (Arzneimittelgesetz - AMG) and the ordinances derived from the AMG are applicable to both types of medicinal product. The legal requirements relating to the manufacture, authorisation, marketing, dispensing and proper use of these medicinal products in respect of oral medication are dealt with in detail. Pursuant to Section 13 AMG, companies that manufacture medicated feedingstuffs require a manufacturing licence. To take into account the special features of these medicinal products, specific stipulations have been laid down regarding the manufacture and dispensing of medicated feedingstuffs by these companies. The use of medicated feedingstuffs is for various reasons in steep decline, while oral ready-to-use medicinal products are, according to reports on practice in the relevant sector, increasingly being used to treat animal stocks as well. When dispensing veterinary medicinal products, the veterinarian must comply with the state of the art and make sure that the animal keeper is able to use the drugs properly. In order to react to doubts regarding compliance with these legal requirements, recommendations for use of oral medication should be developed which provide veterinarians with an aid to assist them in deciding which type of drugs are most suited for the respective case, and what is to be complied with in their use. The recommendations for use are intended to facilitate the correct application of oral medication in respect of both types of veterinary medicinal product.     

Voluntary testing procedures of farm animal housing equipment according to the Animal Welfare Act of 1998]

Before its broad application in practice, housing equipment should be tested, in particular with regard to animal welfare. The differing positions of the German Federal Council (Bundesrat) and the German Federal Parliament (Bundestag), whether such testing should be mandatory or voluntary, have been conciliated in the amended animal welfare act by empowering the Federal Ministry of Food, Agriculture and Fisheries (BML) to fix official standards for voluntary testing procedures by regulation. On request of the BML, a report as scientific basis for a draft regulation is currently prepared by the scientific animal welfare committee of the German Agricultural Society (DLG). The scientific animal welfare committee has been appointed by the DLG in order to provide support in the effort to strengthen animal welfare aspects in the DLG-utility testing procedure of housing equipment, which is in place since 1953. The committee elaborates standards concerning testing methods, assessment criteria and the necessary size of investigations. As required, the scientific animal welfare committee may support the DLG-testing bodies in the implementation of the animal welfare part of the testing procedure. It will, moreover, be involved in the welfare assessment based on the testing results. The amendments of the already established testing procedure will help to fulfill the general requirements on an acceptable animal welfare testing procedure. While keeping in mind that there are certain limits in what can be achieved by a voluntary testing procedure, the enhanced consideration of animal welfare aspects within the DLG-utility testing procedure has the advantage to be relatively unbureaucratic and in line with EU legislation, and is, therefore, an appropriate tool for a contibrution to improved animal welfare in livestock housing.     

The role of behavioral science in animal welfare in teaching and practical application

This paper gives an introduction on the importance of ethology as a basis for the ethical animal welfare. The last edition of the Animal Welfare Act of the Federal Republic of Germany is based on the ethological principle which includes, that the animal must be free to satisfy its needs and preserve itself from damage by using of adequate behavioural patterns. With the help of observing animal behaviour the veterinarian can remark faults in the animal management before pain, suffering or injuries set it. So the importance of the ethology in the system of veterinary education is clear. Pertinent information shall promote the dialogue between scientists working in the field of animal behaviour and people engaged in animal welfare.     

Amendment of the Animal Welfare Act and other topical questions in animal welfare legislation]

A report on the amendment of the German Animal Welfare Act as well as on other questions relevant to animal welfare legislation in the Federal Republic of Germany is given.     

Mathematical modeling and simulation in animal health. Part III: Using nonlinear mixed‐effects to characterize and quantify variability in drug pharmacokinetics

A common feature of human and veterinary pharmacokinetics is the importance of identifying and quantifying the key determinants of between‐patient variability in drug disposition and effects. Some of these attributes are already well known to the field of human pharmacology such as bodyweight, age, or sex, while others are more specific to veterinary medicine, such as species, breed, and social behavior. Identification of these attributes has the potential to allow a better and more tailored use of therapeutic drugs both in companion and food‐producing animals. Nonlinear mixed effects (NLME) have been purposely designed to characterize the sources of variability in drug disposition and response. The NLME approach can be used to explore the impact of population‐associated variables on the relationship between drug administration, systemic exposure, and the levels of drug residues in tissues. The latter, while different from the method used by the US Food and Drug Administration for setting official withdrawal times (WT) can also be beneficial for estimating WT of approved animal drug products when used in an extralabel manner. Finally, NLME can also prove useful to optimize dosing schedules, or to analyze sparse data collected in situations where intensive blood collection is technically challenging, as in small animal species presenting limited blood volume such as poultry and fish.     

Evaluation of efficacy of heartworm preventive products at the FDA

The Center for Veterinary Medicine, U.S. Food and Drug Administration (FDA/CVM) has authority under the United States Code 21 under Section 514.80 to monitor for adverse experiences of approved animal products. Although veterinarians voluntarily report suspect drug-related events to manufacturers, firms that market FDA-approved animal products must report serious events to the FDA within 15 working days of the veterinarian or pet-owner's call to them. Under the present regulations, canine heartworm preventatives are approved for 100% efficacy after testing in laboratory and field conditions. The report of lack of efficacy against heartworm larvae is a serious adverse drug event because the resulting condition or the treatment of the condition is life threatening. Information on lack of effect that are deemed possibly, probably, or definitely drug-related available for review under generic product on the FDA/CVM website Surveillance of these reports indicates there are some failures for virtually all heartworm prevention product categories. Most failures have been reported in heartworm-endemic states. At this time, it is unclear whether these are representative of the rare occurrences of failure that have been in existence for a long time, but not reported regularly or promptly, or whether there is a true increase in complaints of ineffectiveness and real variability between products. This paper discusses methods, personnel, and procedures in place in the Division of Surveillance that will aid the FDA to better assess heartworm preventive treatment failures. It discusses scoring paradigms presently utilized by FDA/CVM to assess severity of complaints of lack of efficacy against heartworms, and welcomes audience input as to how to improve existing processes. Results suggest that more comprehensive reporting will provide FDA/CVM more accurate surveillance information regarding efficacy problems. Such practices will permit FDA/CVM to better interpret both incidence and severity of in-effect and possible patterns of emerging resistance and to convey this in any necessary updated labeling. It also indicates that as part of that process, practitioners should return to a more conservative testing schedule.     

Animal health: foundation of a safe, secure, and abundant food supply

During the past century, reductions in animal diseases have resulted in a safer, more uniform, and more economical food supply. In the United States, the passage of the 1906 Federal Meat Inspection Act mandated better sanitary conditions for slaughter and processing, as well as inspection of live animals and their processed products. Following World War II, Congress passed the Poultry Products Inspection Act. Both acts are regulated by the Food Safety and Inspection Service (FSIS) of the US Department of Agriculture (USDA). The USDA's Animal and Plant Health Inspection Service (APHIS) is responsible for regulations governing the health of live animals prior to slaughter. This article is a brief overview of the ways in which the current predominance of zoonotics among emerging diseases underscores the importance of veterinary health professionals and the need for continued coordination between animal-health and public-health officials. Examples of intersections between animal- and public-health concerns include bovine spongiform encephalopathy (BSE) and Johne's disease, as well as extending beyond food safety to diseases such as avian influenza (AI). In the United States, we have in place an extensive public and private infrastructure to address animal-health issues, including the necessary expertise and resources to address animal-health emergencies. However, many challenges remain, including a critical shortage of food-animal veterinarians. These challenges can be met by recruiting and training a cadre of additional food-supply veterinarians, pursuing new technologies, collaborating with public-health officials to create solutions, and sending a clear and consistent message to the public about important animal-health issues.     

Ethological basis for the evaluation of animal welfare in housing systems for agricultural animals and laboratory animals]

The Swiss Federal Act on Animal Protection (1978) requires the sale of mass-produced housing systems for farm animals to be authorized by the Federal Veterinary Office. Authorization is only granted for housing systems that safeguard the animals' welfare. A concept for the assessment of Animal Welfare has to provide a high forensic value. The capacity of farm animals to adapt to an intensive housing system can be directly examined, whereas the existence and extent of subjective feelings can only be assumed. In our concept the examination focuses on the interaction of individuals with their artificial environment. The main question is whether or not the individuals are able to cope with given nonspecific (e.g. temperature, humidity) and specific (e.g. drinking troughs, behaviour of conspecifics) stimuli in order to reach the immediate (e.g. drinking, make way for) and ultimate (survival, reproduction success) goals. Animals of the same breed are observed in a highly diverse environment in order to determine normal behaviour. Whether behavioural expressions which differ significantly from normal behaviour are adaptive to the restrictive housing conditions is judged by the behaviours' consequences for both, the individuals and the environment. Many studies prove the concept's high forensic value and the authorities prefer conclusions based on this concept to others referring to the animals' motivational and emotional state. However more research has to be done with respect to animal welfare in farm and laboratory animal breeding as well as in the use of laboratory animals for experimental studies.     

The first Polish animal contagious disease act of 1844

The Veterinary Control Act of 1844 was the first to regulate in entirety the control of infectious diseases in animals and questions of sanitary inspection of animal food products in the Kingdom of Poland. The act listed explicit procedures regarding diagnostics, control and eradication of diseases as well as concerning animal food product inspection. The act required that animal owners become familiar with symptoms of animal diseases, their methods of control and that they prevent their spreading. The obligations of veterinarians, state physicians and administrative control bodies in the control of animal diseases were specified by the act. Besides the main text on the control of diseases and meat inspection the act also contains elements of food law, some norms concerning public law and order (e.g. requirements concerning dogs) and even some regulations on animal protection.     

Availability, brands, labelling and salmonella contamination of raw pet food in the minneapolis/st. Paul area

The purpose of the study was to characterize the commercially available raw meat pet food diets in the Minneapolis/St. Paul area by (i) determining the number and types of available diets; (ii) assessing pet food stores and brand labels for the provision of precautionary statements regarding the risk of foodborne illness from raw meat; (ii) assessing the labels for Food and Drug Administration (FDA)/American Association of Feed Control Officials (AAFCO) required content and nutrient-related information; and (iv) culturing purchased diets for the presence of Salmonella. Sixty raw meat diets were purchased, representing 11 different brands from eight different stores. Diets were readily available in the form of raw-frozen, dehydrated or freeze-dried varieties from different protein sources, such as lamb, beef, chicken or duck. All stores promoted raw meat diets; however, none provided foodborne illness warnings. Brands varied greatly in their precautionary statements; none of the diets underwent feeding trials; and nutritional adequacy substantiation was through formulation only. The first five ingredients tended to consist of meat, organ meat (by-products), vegetables, grains and ground bones. Currently, it is required that pet foods have an AAFCO nutritional adequacy statement and provide a guaranteed analysis table. Three brands did not meet these FDA requirements. Thirty-one (51.7%) of the 60 raw meat diets underwent some degree of processing including dehydration, freeze-drying or high-pressure pasteurization. Four of the 60 raw diets (7%) tested positive for Salmonella. Analysis of raw meat pet food labels indicated a lack of foodborne illness warnings. Based on these findings, we recommend that warning statements similar to those required by the United States Department of Agriculture and placed on labels of raw meat intended for human consumption be provided on the labels of raw meat pet food diets.