The Recent Discoveries of Nitrosamine Impurities (PDA/FDA Joint Regulatory Conference 2023)

Sander Van Gessel, MEng, Business Unit Director, DFE Pharma, discusses the recent findings of nitrosamine impurities in human drugs as a part of his session, "Reducing Nitrosamines Without the Use of Scavengers: The Critical Role of Excipients - An Excipient Manufacturer's View."

Van Gessel: So, since 18, there's been a lot of investigation into nitrosamines as a potential carcinogenic, yeah can impact drug safety. So naturally across the supply chain of drug manufacturer, the partners within the industry have all been looking at it, including players like DFE pharma, supplying decisions to the industry. And we're continuously investigating and, you know, one of the challenges that we as an industry have also needed to overcome is, you know, also looking at the analytical techniques that are necessary to not only detect the nitrosamines in the end product, but also the potential root causes of those nitrosamine formations in the entire supply chain.

Van Gessel: There are a lot of potential root causes of nitrosamine impurities. And we've been studying this since 2018. A lot of the suppliers of raw materials, such as excipients, have been looking at nitrosamine levels with in their products that can lead to those nitrosamine impurities in in drug, end product drugs. I think you know, for most reliable reputable suppliers, this is now pretty much under control. To take the pharma as an example, we've studied the nitrosamine levels in our excipients, and they're all below two ppb parts per billion. To put parts per billion into perspective to control a football field... It's like controlling a football field to 10 particles of sand to get to that two ppb level. However, the industry has moved on a little bit from nitrosamines to actually looking at what are potential causes of nitrosamines being created in the end product itself. And over here, the research is into the pathways leading to nitrosamine creation in the end product after it's been manufactured. If we look at what what's happening there we have, for example, nitride impurities, which are within different raw materials that can react with a means in certain API's to create nitrosamines over time and product.