An Overview: Nitrosamine Impurities in Medications and Its Regulations
What are Nitrosamine compounds?
Nitrosamine compounds are an essential part of the pharmaceutical sector. They are a group of compounds, mostly carcinogenic, formed from nitrites and secondary amines. Nitrosamines were discovered in many consumer products Nitrosamines can also be formed during the manufacturing of pharmaceuticals, which begs the question of regulating and controlling them in the pharmaceutical industry and consumer products.
Nitrosamine impurities in drug products?
According to many ongoing and previous animal studies, nitrosamine impurities are probable human carcinogens, i.e. cancer development impurities. Long-term exposure to unsafe levels of nitrosamine impurities poses the risk of cancer in human subjects.
Consumer products and foods such as meats, dairy products, vegetables, cigarettes, as well as drinking water also contain varied levels of nitrosamines.
The studies suggest that low levels of nitrosamine impurities in the medications do not pose any immediate health risk with the use of drugs.
Health threat caused by Nitrosamine impurities varies from person to person, depending upon factors such as:
● The daily dose of the drugs.
● The medication intake duration.
● The level of the nitrosamine impurity in the drug.
If the Patients feel uncomfortable after a certain period of taking medication containing nitrosamine impurities, they should consult healthcare providers before stopping a prescribed medication, instead of not treating the condition.
FDA recommendations to reduce nitrosamine in drug products
FDA has provided drug manufacturers with a recommended framework for a risk-based safety assessment of nitrosamine drug substance-related impurities (NDSRIs) that could be potent in high levels in products already existing in the markets, and as well as in products under development and/or review by the agency
Quality risk management principles as outlined in ICH Q9 must be used to conduct risk-based safety assessments. Regulations to limit human exposure to nitrosamine impurities from drugs will undergo updates over time.
Alternative Methods to reduce nitrosamine in drugs
Ascorbic Acid
it has been observed that the usage of ascorbic acid (Vitamin C) or alpha-tocopherol (Vitamin E) reduces the presence of nitrosamine impurities.
Antioxidants and Amino Acids
Antioxidants and amino acids in oral dosage forms are effective in preventing the formation of impurities.
Sodium Carbonate
The use of excipients such as sodium carbonate is yet another method that has been highlighted by the FDA in curbing the formation of nitrosamine impurities in drug products
The FDA has issued regulations to the manufacturers to identify the benefits of the alternative approach and demonstrate its effectiveness to the agency.
From our understanding, the stance that nitrosamine impurities pose major health risks to people via drugs is clear. Therefore, these impurities have become a focus of global regulatory agencies, including the FDA, and other healthcare authorities are taking measures to prevent unsafe levels of impurities in other drug products. Significant Regulatory changes are undergoing, and manufacturers need to be aware of the latest updates in regulation. We will help you with every regulatory procedure and enlighten you on its updates, contact us for a compliant strategy.
