Over the past eight months, more than a dozen pharmaceutical distributors around the world have voluntarily recalled hundreds of batches of generic versions of the drug valsartan and related products losartan and irbesartan, which are commonly prescribed to treat high blood pressure and heart failure. According to the Agency for Healthcare Research and Quality, about 1.6 million people purchased valsartan in the US in 2016. The recalled products contained active pharmaceutical ingredients (APIs) with trace amounts of either N-nitrosodimethylamine (NDMA) or N-nitrosodiethylamine (NDEA), which are both probable human carcinogens. Testing by companies and the US Food and Drug Administration has revealed that the impurities came from multiple API manufacturers, facilities that synthesize the biologically relevant compounds—valsartan and related sartan molecules—and then sell them to companies that make the final tablets that reach consumers. Nitroso impurities are very well studied and documented in food industry and drinking water specifications worldwide. However, their origin and impact were not studied or extrapolated in pharmaceutical substance manufacturing processes. In this presentation, the synthetic pathway for the formation of the Nitroso compounds along with the possible control to reduce the formation of these impurities will be discussed.
upon completion , participants will be able to Learn the fundamentals of mutagenic and genotoxic impurities
upon completion , participants will be able to understand the formation of nitroso compounds
upon completion , participants will be able to learn how to conduct risk assessment
upon completion , participants will be able to learn how to establish control to eliminate the formation of nitroso compounds