Safety Toxicology. During the lengthy process of drug development, comprehensive tests need to be carried out to analyse organ toxicity. This includes mandatory tests in different animal species such as rodents and dogs (mainly for liver and kidney toxicity). Such tests must comply with specifications stipulated by the FDA, the ICH and the EMA. Besides acute toxicity, long-term toxicity, toxicokinetics and pharmacokinetics, and organ toxicity have to be tested to detect potential side effects on the cardiovascular and nervous systems, the lung, liver and kidney.

FDA’s Critical Path Initiative and the Innovative Medicine Initiative foster research to identify novel biomarkers that can predict organ damage early on. Tests for such markers are likely to become recommended for the approval of new drugs.

Translational safety biomarkers (SIGNATOX).

SIGNATOPE is currently developing immunoassays for drug-induced kidney and liver injury. The testsystem is the only method capable of quantifying identical protein biomarkers in all species using identical tests in the preclinical and clinical phases. Standardized cross-species assays will streamline test procedures in pre-clinical and clinical development and make cross-validation of different tests obsolete.





alfa-microglobulin binding protein X X X X X
Aquaporin 2 X X X X X
Clusterin X X X X X
Cystatin C X - - X X
Klotho X X X X X
Nephrin (NHPS1) X X X X X
Podocin (NHPS1) X X X X X
Retinol Binding Protein 4 X X X X X
Synaptopodin X X X X X
Osteopontin X X X X X


Gautier, J. C., Zhou, X., Yang, Y., Gury, T., Qu, Z., Palazzi, X., Leonard, J. F., Slaoui, M., Veeranagouda, Y., Guizon, I., Boitier, E., Filali-Ansary, A., van den Berg, B. H., Poetz, O., Joos, T., Zhang, T., Wang, J., Detilleux, P., and Li, B. (2016) Evaluation of novel biomarkers of nephrotoxicity in Cynomolgus monkeys treated with gentamicin. Toxicology and applied pharmacology 303, 1-10