The authors explore the idea that there could be a possible manner in which nitrosamines could come into existence - by means of different phases within the manufacturing procedure.
One of these stages involves wet granulation, which could enhance the interaction between the API and substances capable of generating nitrosamines.
Moreover, certain manufacturing techniques like fluid-bed drying, which rely on the utilization of significant volumes of air, might also contribute.
The reason behind this is that these processes have the potential to expose the combination of the drug product to compounds of nitrogen oxide (NOx), which could potentially undergo a conversion into nitrous acid.
probably - that’s the “problem reference” that raised the concern over the Ames test (though I cannot state strongly enough the tests they did weren’t at modern standards), so if I refer to Rao et al without further details that’s the one
I appreciate your detailed analysis of the differences in FDA’s guidance document compared to those of HC and EMA. Your insights highlight significant points of clarity and divergence.
I acknowledge the outlined timeline for incorporating NDSRIs into risk assessments and confirmatory testing. It’s crucial that manufacturers reevaluate within 3 months and complete by November 1, 2023. Submission of changes should be done by August 1, 2025, meeting AI limits.
The Complete Response Letter(CRL) requested additional information on nitrosamine impurities to be tested for based on new draft guidance issued after the neffy(epinephrine nasal spray) NDA submission, according to the article.
