Evaluating Nitrosamines from Elastomers in Pharmaceutical Primary Packaging

Abstract

Nitrosamines have gained unexpected attention again, triggered by their discovery at significant concentrations in some active pharmaceutical ingredients and pharmaceutical products. Regulatory agencies not only expect the marketing authorization holders to include a nitrosamine risk assessment in their drug development process but to also apply it retrospectively to the marketed drug product. As part of this risk assessment, all possible sources of nitrosamines need to be evaluated. This review provides the chemical background of nitrosamines and elastomeric formulations, the current regulatory status in the pharmaceutical and other industries, and discusses analytical challenges of nitrosamine measurement. This evaluation of elastomeric components as a potential nitrosamine source proposes how this information can be used in a drug product risk assessment.