I hope our community can help answer this very interesting question coming from one of our members (@Ghada.Saad) , and especially important for Small and medium organizations.
I am working in a pharmaceutical company in Egypt. I would like to know more about how nitrosamine issues are handled in small and medium sized pharmaceutical companies. Is it through multidisciplinary committees?? Are there dedicated teams?? Which department is the leader?? What are the most important reaources?? It would help me a lot to speed up implementing nitrosamine risk assessment in my company
Thanks for raising an interesting question. As a GMP inspector, I would prefer to see more of a holistic approach regardless of the size of the organization. It is like implementing quality risk management principles in your organization that cannot be adequately implemented without a cross-functional team. The personnel having an in-depth understanding of the manufacturing process of DS/DP (from product development, production and packaging), analytical challenges by quality control including validation team, current regulatory requirements (usually best known by QA), technology transfer including regulatory affairs personnel should form a core of the cross-functional team. In addition, you may invite other subject matter experts on a case by case basis. Based on my inspection experience since the issue of nitrosamine has surfaced up (June 2018), usually, the discussion is led by the QA and supported by other departments. Having said that, there is no right or wrong, if you wish another department (s) to lead the discussion. It is important to note that risk assessments should be performed on the manufacturing site(s) and marketing authorization holder(s) (MAHs) should have appropriate oversight as ultimately they are responsible for the quality and safety of the DS/DP.
Finally, the ultimate objective of nitrosamine risk assessment is to find the potential root causes in DS, DP, excipients, packaging materials etc and implement mitigation strategies. The proposed changes to the manufacturing process need to be discussed with respective NRAs before implementation and change management principles are followed and documented.
The above are my personal views for your consideration, please.
@Naiffer_Host Thank you very much Dr for raising up this issue. And thank you @Vimal for your contribution and insights.
Well I think some challenges that we face in our attempt to apply nitrosamine risk assessments are:
When we request drug master files from drug substance manufacturers, some do not provide the complete synthesis method.
Analytical instruments like GC-MS LC-MS HPLC-MS are still scarce…
We are looking for a simple analytical method for analysis of nitrites, nitrates…