Navigating the landscape of Nitrosamine Concerns and FDA Mitigation Strategies
Nitrosamine impurities are found in certain products and are known as probable human carcinogens. If these drugs are taken regularly over a certain period, they could increase the risk of cancer.
After the discovery of these impurities, in June 2018, the FDA brought attention to products that contain high amounts of nitrosamine.
Valsartan, a drug that is used to treat high blood pressure was recalled from the market as it contained a high amount of nitrosamine impurities.
After this revelation, it has been discovered that nitrosamine formation occurs in other common drug products used for the treatment of heartburn and type 2 diabetes.
Impurities caused by nitrosamine were the top priority of the pharma industry and it led to legal compliances for drug manufacturers to present their plans to mitigate risks.
After that in September 2020, the FDA issued guidelines for the industry to help ensure the safety of the drug supplies. FDA issues a three-step mitigation strategy that drug product manufacturers will follow to prevent high levels of nitrosamine impurities in different pharma products.
Similar to the FDA, EMA also started risk assessment procedures to meet new guidelines.
The Formation process of Nitrosamine impurities
Nitrosamine impurities in drugs take place when nitrite and vulnerable amines (Specifically Secondary amine) are present in high volume. For nitrosamine formation there is essential to presence of functional groups susceptible to nitrosamine formation, such as secondary amines, or the presence or in situ formation of a nitro sating agent – like a nitrous acid – from nitrite.
Drug products most at risk of nitrosamine formation are those that contain active pharmaceutical ingredients (APIs) whose structure consist of secondary or tertiary amines, or tertiary ammonium salts. There is also a risk in drugs where the active is stabilized by buffers containing tertiary or quaternary amines and in drug products where any excipient contains secondary or tertiary amines or quaternary ammonium salts.
An FDA-recommended mitigation strategy
To reduce the risk of impurities in drugs, the FDA suggested a mitigation strategy that details adding antioxidants such as ascorbic acid, or alpha-tocopherol, to drug formulations as excipients.
Among many nitrosamine inhibitors, focus is placed on ascorbic acid, which reacts with several nitrosating agents.
ascorbic acid and alpha-tocopherol are known as antioxidants that can block nitrosation reactions and significantly reduce or prevent the formation of nitrosamines.
Therefore, these two offer formulators safety to redesign their drug products to reduce the risk of nitrosamine formation.
Develop Risk-Free Formulations with us
We know that complying with the new regulatory requirements concerning nitrosamine impurities formation in drug products comes with entirely new sets of challenges.
We are in this innovation space of the pharmaceutical industry, and we possess the solutions to tackle these emerging issues.
Together, we can ensure that your pharmaceutical products are safe for human use. To learn more about our quality ingredients and expert services, visit our website and explore opportunities to develop nitrosamine-free pharmaceuticals drugs and other products.
