Information required animal studies

All pharmaceuticals marketed in the United States, including biotechnology products, must be proven safe and effective for their intended use. The FDA requires that all recombinant proteins and other biotechnology products be produced by a manufacturer holding a certified Biologic License Establishment (BLE). The pharmaceutical company is required to collect safety and efficacy data, first in animal studies and subsequently in clinical trials. This information is submitted in a new drug... 

Once the animal studies are completed human studies can commence, moving through phase I (up to 50 naive patients to establish a sufficient immune response) phase (several hundred patients in several locations) to phase III in which expanded studies on as many as thousands of patients. The trials require to be randomized and closely controlled by being blinded to avoid bias in interpretation. The patients all have to provide informed consent and strict adherence to good clinical practices in accordance with ethical principles is required to ensure risk-benefit considerations justify the risks associated with all trials of this type. The safety of the patients is an overall requirement and trials must be supervised by the appropriate independent ethics committee or the local Institutional Review Board. 

The assessment of human cancer risk associated with a substance is a complicated scientific endeavor requiring careful review of all pertinent information by professionals. Such assessment involves primarily the evaluation of clinical, epidemiological, and animal studies as well as short-term tests, structure activity, comparative metabolism pharmacokinetics, and mechanism of action when possible. 

Dermal Exposure Levels. Setting acceptable maximum dermal exposure levels to specific pesticides has been difficult. This is primarily due to a lack of specific data on dermal transport rates for specific pesticides as related to adverse effect levels and presumed no-effect levels. We are now requiring such data from the registrants, and our Department has a suggested protocol (1) that is offered to registrants that will provide such information from animal exposure studies. This dermal transport rate information is important in setting minimum field reentry intervals for field workers as well as in evaluating exposure levels of mixers, loaders, and applicators. 

However, in tests of chemicals with unknown toxic characteristics, problems often arise because the actual responses of animals differ widely from those anticipated when the study was designed. To address this problem, it is prudent to increase the number of animals to ensure that animals are available at key points of a study to provide adequate information. In acute studies, the requirement for groups and number of animals in groups is related to the reliable determination of acute toxic effects and the estimation of a median lethal dose. In subchronic and chronic testing, the numbers are related to the detection of effects, providing sufficient animals for an acceptable investigation of toxic mechanisms and giving an indication of a no-effect level. ... 

With respect to studies in animal models which dissect the mechanisms of formation, localization, and fate of immune complexes, the mechanisms by which they elicit an inflammatory response, and their biologic activities, we provide little more than summary information required to understand the concept of immune complex disease and the principles of the tests. For more detailed information, the reader is referred to several excellent reviews (C14, H2, Til, Ul, W12). 

The information required to evaluate specific target organ/systemic toxicity comes either fi om single exposure in humans, e.g. exposure at home, in the workplace or environmentally, or from studies conducted in experimental animals. The standard animal studies in rats or mice that provide this information are acute toxicity studies which can include clinical observations and detailed macroscopic and microscopic examination to enable the toxic effects on target tissues/organs to be identified. Results of acute toxicity studies conducted in other species may also provide relevant information. 

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