United States repeat-dose studies

In addition to rodent studies, regulatory guidelines for pharmaceuticals require that repeated dose safety studies of up to nine months (in the United States, six months elsewhere) in duration be conducted in a nonrodent species. The most commonly used nonrodent species is the dog, followed by the monkey and pig. Another nonrodent model used to a limited extent in systemic safety evaluation is the ferret. The major objectives of this chapter are (1) to discuss differences in rodent and nonrodent experimental design, (2) to examine the feasibility of using the dog, monkey, pig, and ferret in safety assessment testing, and (3) to identify the advantages and limitations associated with each species. 

TABLE 5.2 Duration of Repeated Dose Toxicity Studies to Support Phase I and II Trials in the European Union and Phase I, II, and III Trials in the United States and Japan ... 

Box 3.2 shows the toxicity package t)q)ically generated before a Phase I trial. These trials are usually conducted in males, and thus do not require formal reproductive toxicity studies. In the United States, women can be included in early trials without any animal reproductive toxicity if special precautions are taken to ensure that pregnancy does not occur. A histopathological assessment of the effects of the test compound on the male reproductive tract is made in the repeat-dose toxicity tests. 

Table 6.1 Duration of repeated-dose toxicity studies to support phase I and phase II clinical trials in the EU and phase I, II and III clinical trials in the United States and Japan3...

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