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Project background

Rodents have a pretty long standing as first-line animal species in immunotoxicity assessment. Indeed, from the pioneering interlaboratory validation studies conducted by the US National Toxicology Program in B6C3F1 mice, and the International Collaborative Immunotoxicity Study (ICICIS) in rats, until the most recent ICH recommendations, rodent studies have been, and still are the 'traditional' benchmark for the preclinical evaluation of the immunological safety of human pharmaceuticals.

Importantly, one general principle of the ICH S8 guideline is that the immunotoxic potential of any new human pharmaceuticals should be assessed, and this is globally in agreement with recommendations of the ICH S6R1 guideline on biologicals. Accordingly, there is a growing need to confirm early rodent findings during longer term non-rodent repeat-dose toxicity studies to improve the reliability/relevance of translating immune changes from animals to human subjects. Conventional rodents often have limited relevance to assess the immunological safety of biologicals, especially humanized biologicals. The dog is a potentially valuable non-rodent species for immunotoxicity evaluation, but is as yet not fully validated. Non-human primates (NHP) have been increasingly used over the last decades despite limitations regarding available understanding of normal and pathological immune responses in NHP. Last but not least, uncertainties regarding future procurement of NHP, especially in Europe, are a matter of growing concern. 

The EU Framework-6 RETHINK project generated a wealth of information showing that minipigs are a relevant animal model in regulatory toxicology. Minipigs have indeed been increasingly acknowledged and recommended for use in a variety of preclinical safety studies. However, only scarce data are currently available regarding minipig use for the evaluation of immunological safety .