Frank Sistare, Ph.D.
- Apr 12, 2017
- Topic: “Aligning Regulatory Agencies and the Pharmaceutical
Industry toward Reducing Toxicity Associated Drug Development
Costs, Timelines and Attrition:
1) Reducing 2 yr Rodent Carcinogenicity Testing
2) Deploying Novel Models to Improve Liver Safety Prediction"
- Date: Friday, October 27th, 2017
- Time: 9:00am
- Place: B448 Life Science Bldg
(1) The 2-yr rodent carcinogenicity study, involving the use of both rats and mice, is the
longest, largest, and most costly animal toxicology study conducted in pharmaceutical
development. Recently, PhRMA industry members have leveraged decades of internal
experience to define a revised testing strategy that allows earlier recognition of drug candidates
devoid of human carcinogenic risk, eliminating the value of conducting a 2-yr rat
study. International negotiations with regulatory agencies were launched along with a
prospective confirmatory testing period to evaluate rat carcinogenicity studies conducted
between 2013-2018 before adopting the approach, which is anticipated to eliminate 40-
50% of such studies.
(2) Drug-induced liver injury is one of the most poorly predicted human risks based on the
results of conventional animal toxicology studies, and as a result, such poor safety prediction
has historically resulted in late stage drug attrition or market withdrawals with the
most devastating effects on human safety, drug development costs and delays. Recently,
improved in vitro and in vivo translational liver models and endpoints have been introduced
and are showing tremendous promise toward improving early de-risking for human
liver safety, but widespread alignment and adoption toward consistent implementation
will require similar data sharing, collaboration, and leadership.