🤷‍♂️ FAQ: How do I calculate the CPCA of my Nitrosamine Impurity?

[Yosukemino]

Difference of guidance between EMA and FDA

FDA - Recommended Acceptable Intake Limits for NDSRIs Guidance for Industry

Some things I noticed right off the bat about differences with other guidance documents which are important: • FDA says to provide a “scientifically justified rationale” if the CPCA is not met. However, they lack the clarity HC and EMA had. o No mention on what to do with a negative Ames. They mention the EAT protocol, but what do you do with a negative? EMA and HC says TTC is appropriate. o No mention of what to do with a negative in vivo study. EMA and HC says apply ICH Q3A/B. o The re…

FDA - Recommended Acceptable Intake Limits for NDSRIs Guidance for Industry

My contributions to the highlights of the guidance: Overall, the U.S. FDA approach is harmonized with the EMA’s guidance on NDSRI detection and mitigation. The updated EMA guidance introduces a new Carcinogenic Potency Categorization Approach (CPCA), which is a basis of the new approach both regulators are taking to determine the AI of a given NDSRI and aid in risk assessment for various APIs. Manufacturers of approved or marketed drug products should, if they have not done so already, eva…