Updated Information
Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities (NDSRIs)
Recommended AI Limits for Certain NDSRIs
Based on Predicted Carcinogenic Potency Categorization for APIs at Hypothetical Risk of Forming Such NDSRIs
APIs that contain secondary amine or dimethyl tertiary amine centers are at risk of forming NDSRIs by nitrosation of the amine center. This can occur under conditions related to the formulation and manufacturing process for the drug product, such as by reaction with residual nitrites in excipients used to formulate the drug product. Table 1, below, presents NDSRIs that can hypothetically form by this process from a number of amine-containing APIs. Recommended AI limits for these hypothetical NDSRIs based on the predicted carcinogenic potency categorization approach are also presented
Table 1: FDA Recommended AI Limits for Certain Hypothetical NDSRIs
Based on Predicted Carcinogenic Potency Categorization
@Naiffer_Host: I’m providing here the Excel files as 04-Aug-2023 with additional structural information and SMILES.
If someone in the community knows
to run data queries, we could utilize Chem Pub to return the maximum daily dose for each compound and calculate the analytical limit. Anyone?
NDSRIs list in FDA as 04Aug23 -Nitrosamine Exchange.xlsx (2.6 MB)