As part of the BioPharma Asia webinars series, Ward d’Autry will share some interesting insights in extractables and leachables qualifications for pharmaceutical primary packaging, regarding N-Nitrosamine assessments. The webinar will be accessible through the BioPharma website; register below.
Recently there have been a number of drug product recalls due to the unexpected presence of N-Nitrosamines. While in most of those cases, N-Nitrosamine formation occurred at the level of the drug substance synthesis and stability, it is well known and documented that some materials, used in primary packaging can also be a source for N-Nitrosamine contamination of the packaged drug product (e.g. older grade elastomers and nitrocellulose laminated blister foils). The unanswered question is: do we know everything about the materials of construction of a container closure system and their ability to generate N-Nitrosamines?
When looking at the formation mechanism of N-Nitrosamines, it are secondary amines (and potentially tertiary amines) that are a precursor to N-Nitrosamine formation, together with a nitrosating agent (such as e.g. nitrite/nitrous acid). When evaluating the extraction profile of materials of construction, it is clear that secondary amines are often encountered as an extractable being present in the material. Should this raise a “red flag” for those materials in a N-Nitrosamine risk mitigation strategy, as one precursor for N-Nitrosamine formation is obviously present in the material? And what could be the consequence of these findings, both for the design of extractable and leachable studies, as well as in the assessment of the E/L-results?
This presentation will give more insights on how an integrated approach for both the E/L-qualification as well as the N-Nitrosamine risk evaluation for a pharmaceutical container closure system could look like.