Conduct of Shorter Duration Carcinogenicity Study using Transgenic rasH2 Mice
Challenge:
- USFDA has recently approved substitution of the traditional 2 year (78 weeks) rodent Carcinogenicity Study with a 6 month (26 weeks) study in the rasH2 transgenic mice.
- This is based on the propensity of these knock-out mice to develop tumors earlier in their lifespan, thus shortening the overall duration of the study.
Solution:
- The team developed systems and processes to handle sensitive transgenic mice
- There was no undue mortality and morbidity, and the positive control data developed for MNU (N-Nitroso-N-Methylurea) and urethane met the validation requirement for development of neoplastic changes. The report was successfully submitted.
This represents a rare achievement in preclinical tox testing only a handful of labs in the world have experience in performing this type study.