Toxicity testing preclinical safety pharmacology

Some biotechnologically derived pharmaceuticals will cross-react with species that can be evaluated toxicologically, while others cross-react only with nonhuman primates such as the chimpanzee, a protected species. In this case, a well-designed safety, or Phase 0 study at doses higher than the proposed clinical dose may provide valuable safety information. However, a lack of cross-reactivity with any nonhuman species does not necessarily make preclinical safety evaluation impossible, not does it limit toxicity testing to species in which the protein lacks relevant pharmacological activity. Some alternative possibilities are summarized in Table 12.9. 

Notifications or applications for clinical trials are supported by summaries or full reports on the preclinical pharmacology and safety assessment. The kind of safety data (e.g. the type and duration of toxicity tests), which are expected at this time, should correspond to the intended route and duration of application. Data on process details and on the quality of the product are not always required. But it must be kept in mind that clinical trials can only render useful results for the later product registration, if the quality characteristics of the tested product and its method of production are the essentially same as for the final product. If available, clinical data from trials in other countries must also be provided. Protocols for the intended clinical trials are an essential part of the application. 

Safety of the product itself for the target organism, the user (who applies it) or the environment is addressed by a range of preclinical and clinical assessments which depend on the product and its use pattern. The range of safety features to be assessed includes local and systemic tolerance, acute and chronic toxicity, mutagenicity and tumorigenicity, reproductive toxicity, immunotoxicity and, for veterinary medicinal products, also the ecotoxicity. The safety tests will be described in more detail in a separate chapter below on preclinical pharmacological and safety test procedures. 

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