Dear Colleagues,
I would like to seek your advice on the following matter.
In the recently published document “Emerging Scientific and Technical Information on Leachable NDBA and Other Small-Molecule Nitrosamines in Infusion Bags” (August 18, 2025), it is highlighted that large-volume parenteral (LVP) infusion bags may present a potential nitrosamine-related risk.
I am currently performing a risk assessment for an LVP medicinal product.
According to the documentation provided by the manufacturer, the elastomeric component of the LVP packaging system may contain N-nitroso-piperidine (CAS No. 100-75-4) at concentrations below 0.1% (w/w).
In accordance with the EMA guideline “Acceptable Intakes (AIs) established for N-nitrosamines – Appendix 1 to the Questions and Answers for Marketing Authorisation Holders/Applicants on the CHMP Opinion under Article 5(3) of Regulation (EC) No 726/2004 on nitrosamine impurities in human medicinal products”, N-nitroso-piperidine is classified among low-molecular-weight nitrosamines considered probable or possible human carcinogens, with an acceptable intake limit of 1300 ng/day.
However, given that the maximum daily dose of the LVP product is relatively high (3000 mL), the corresponding AET for N-nitroso-piperidine is calculated to be extremely low (0.43 ng/mL).
Considering that this limit is significantly lower than the potential worst-case content indicated in the material documentation, a dedicated extractables and leachables (E&L) study is required.
Could you please assist by sharing suitable analytical methods or validated approaches for the determination of N-nitroso-piperidine in elastomeric materials and LVP infusion systems within E&L studies?
Thank you in advance for your support.