RasH2 Webinar RecapDr. Paranjpe opened with a brief overview of the development and refinement of the Tg.rasH2 mouse model as a tool to evaluate the potential risks of novel pharmaceuticals, including genotoxic and non-genotoxic materials.
He provided compelling data, visual examples, and personal testimony regarding the validity of the Tg.rasH2 mouse model as a substitute for the two-year mouse carcinogenicity study. The following unique advantages were mentioned:
- lack of increasing initial body weights (IBW) and body weight gains (BWG);
- low mortality;
- low incidence of spontaneous tumors;
- no drift in tumor incidence;
- low incidence of lethal degenerative changes and non-tumorous lesions;
- shorter duration of the studies;
- lower number of animals required;
- lower amount of test articles required.
Growing Adoption and Changing ICH Guidelines
– Dr. Madhav Paranjpe
He also noted that the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) S1 Guidelines are expected to undergo a revision in 2019, which he believes will result in a reduction in the number of two-year rat studies. He expects this will also trigger a significant increase in the use of six-month Tg.rasH2 studies, in place of the two-year mouse bioassay.
Standard Study ProgressionIn the webinar, Dr. Paranjpe reviewed the standard progression of studies utilizing the Tg.rasH2, with examples of the study design. Generally, a five-day dose range finding study is followed by a twenty-eight-day dose range finding study, with both studies utilizing rasH2 wild type mice. The dose range finding studies are followed by the six-month carcinogenic study using hemizygous Tg.rasH2 mice.
The following is the standard study design for a six-month Tg.rasH2 carcinogenicity study:
|Number of Animals|
|Group 1 (Vehicle)||0||25||25||5||5|
|Group 5 (Positive Control)||1000|