Permissible limits for impurities during clinical development has always been a grey area. Existing guidelines, specifically ICH Q3A only formally apply to marketed products. How factors such as duration of clinical trials have never been effectively addressed.

Whereas process parameter risk quantification is conducted using mathematical calculations (Monte Carlo simulations) based on a process model, risk analysis is a semi-subjective methodology, of value for both early, as well as for late process development work. Herein we will focus on early process development, when little experimental information is available. In spite of its