Tick Box or Informing Patient Safety: Case Studies on the Value of Chronic Toxicity Studies for Biotherapeutics (S22-2)

While chronic toxicity studies generally have their place in drug development, their routine use in the context of biopharmaceuticals should be reconsidered. Due to their high specificity to the intended target, toxicity is primarily linked to exaggerated pharmacology and/or on-target/off-tissue activity. Therefore, a good understanding of target biology and pharmacology, together with available data from shorter duration (e.g. up to subchronic) studies, can reliably predict any potential for adverse effects. On the other hand, the frequent occurrence of anti-drug antibodies following the repeated administration of a human biopharmaceutical, which is recognized as a foreign protein in animal species, can significantly impact the interpretation of study data. In the best case, this may increase clearance and thus reduce exposure; in the worst case, immune complex formation can lead to severe toxicity and mortality in the animals. The likelihood of immunogenicity in animals, which is not considered predictive of immunogenicity in humans, will inevitably increase with prolonged exposure. In conclusion, a more targeted, risk-based approach to safety assessment may be more beneficial, both from a scientific and ethical standpoint. This presentation will provide a few supportive case studies.