IPEC Federation Position Paper on Role of Excipients in determining N-Nitrosamine Risks for Drug Products - Thoughts?

An informative position paper has been published by IPEC in March 2022 enumerating role of excipients and potential N-Nitrosamine sources in excipients.
202203-if-nitrosamines-position-paper-final-1646123452-1.pdf (235.1 KB)


@DAB thanks for sharing the publication of the IPEC position paper. A couple of items spark my curiosity:

“many excipients contain traces of nitrites that can result in the formation of nitrosamines under specific conditions within the drug product. The IPEC questionnaires (IPEC-Americas Template, IPEC-Europe Template) identify checkpoints, namely the manufacturing process, vulnerable amines, and nitrosating agent, to be assessed.”

How rich has been this information on the DP risk assessment? How comprehensive has been accessing the information on the recent Nitroso-API impurities?

“Rather than removing or limiting nitrites in excipients, the impact of nitrites in a given excipient should be evaluated individually for each drug product for any potential risk. Whether the presence of nitrites in an excipient is a significant risk factor will depend on the components in the drug product formulation” / “the MAH or drug product manufacturer should mitigate any risk in
cooperation with the excipient supplier(s). Here, a limit for nitrites may be appropriate.”

Access to information and close cooperation is a must. How has been your experience?

“Obligation to test – some drug product manufacturers have indicated that an excipient
manufacturer should test their excipients to confirm the absence of nitrosamines and nitrites
or provide typical levels. Excipient manufacturers are under no obligation to test excipients for
these substances. Excipient manufacturers could voluntarily provide such data in cases where
it is deemed to be warranted.”