Carcinogenicity Testing
Long-term animal studies (typically 2 years in rodents) assessing whether a compound causes cancer. Carcinogenicity testing is required for peptide drugs intended for chronic use. The thyroid C-cell tumour finding for GLP-1 receptor agonists emerged from such studies.
Technical Context
Standard approach: 2-year rat study + 6-month transgenic mouse study (p53+/-, rasH2, or Tg.AC models). ICH S1A/B guidance: carcinogenicity testing required when drug will be used continuously or intermittently for ≥6 months, or when there are specific concerns (genotoxicity findings, pre-neoplastic lesions in repeat-dose studies, structural similarity to known carcinogens). GLP-1 RA thyroid C-cell findings emerged from 2-year rat carcinogenicity studies — illustrating the value of long-term rodent testing for detecting organ-specific tumour risk. For biotechnology-derived peptides, ICH S6(R1) notes that standard 2-year rodent carcinogenicity studies are generally inappropriate (species differences in receptor expression and signalling may render results non-predictive). Weight-of-evidence assessment considering target biology, chronic toxicology, and human exposure data may be used instead.