The Predictive Value of Non-Clinical Testing

• Rats and dogs are a common choice of animal model in general toxicity studies (repeated-dose toxicology studies). Except if they are not suited due to pharmacodynamic, pharmacokinetic, and/or pathophysiological differences.

• Rats are often selected for reproductive toxicology studies (that assess the effects on fertility, embryo-foetal development, and pre- and post-natal toxicity).
  
  
• Rabbits are often chosen as a second, non-rodent species for studies that assess the potential for embryo-foetal toxicity. Rabbits may be replaced by non-human primates if the rabbits are not suited for the studies which is often the case for biotechnology products.
  
  
• Rats, mice, or hamsters are common in long-term carcinogenicity studies. Transgenic mice can be used in short-term study designs if additional assessment is needed on carcinogenicity.
  
  
• Other non-clinical study types address specific aspects of safety, e.g. if people can become addicted to the drug (rodents, primates), vaccines (ferrets), immunotoxicity (mice), hypersensitivity (guinea pig), and dermal, topical toxicity (pig).
  
  
• For some studies, the most common animal models can not be used. In these cases, rats can be replaced with hamsters, gerbils, or guinea-pigs and dogs might be replaced by mini-/micro-pigs or monkeys.

Sometimes it is not possible to find a ‘relevant’ and predictive animal species. This is often the case with biologics. In those cases other approaches are recommended. These include the use of relevant transgenic animals which express the human target, or the use of proteins that have the same structural features and gene-patterns (homologous proteins). Researchers are always adviced to include intensive monitoring in protocols. Also, significant safety measurements are needed in the clinical trial setting.