What are Nitrosamines?
According to the European Medicines Agency (EMA), nitrosamines are chemical compounds classified as probable human carcinogens on the basis of animal studies.
EU regulators first became aware of nitrosamines in medicines in mid-2018 when nitrosamine impurities, including N-nitrosodimethylamine (NDMA), were detected in blood pressure medicines known as 'sartans'.
Nitrosamines in food and drugs are formed by reactions of organic amines and their derivatives with nitrosating compounds (like Nitrites and Nitrates. There is a very low risk that nitrosamine impurities at the levels found in medicines could cause cancer in humans.
DFE Pharma perspective
Excipients could contribute to the formation or content of nitrosamines in drug products - either directly or through precursor substances present in the excipient (e.g., nitrites, nitrates, amines, or other nitrogen containing compounds). DFE Pharma has proactively assessed all excipients regarding Nitrites, Nitrates, and Nitrosamines.
Our questionnaires are revised to reflect the 2020 regulatory updates, with reference to the EMA assessment report , the US FDA Guidance and how they may be adapted for pharmaceutical excipients. However, the information also assists companies to address similar requests from other regulatory authorities, based on our current understanding of global activities on this subject.
Your Support on Nitrosamines
Please contact any of your DFE Pharma contacts regarding questions on nitrosamines. We can supply support documentation and safety assessments for all of our excipients with the following information:
- Use of sodium Nitrate or any other nitrosation agent in the manufacturing of our excipients
- Analysis of Nitrite, Nitrate, and Nitrosamine levels of all DFE Pharma products
- Use and origin of water in the manufacturing process
- Potential presence of secondary or tertiary Amines in the excipients
- Use or potential presence of any amide, primary Amines, or ammonium salt
- Use or recovery of nitrogen-containing solvents
- Manufacturing equipment and cross-contamination