Recent trends in Nitrosamines in pharmaceutical industry 2025

Nitrosamines are a class of chemical compounds that are generally formed when nitrites or nitrates react with amines under certain conditions, such as high temperatures or acidic environments.

Here are the key points to be taken into consideration for nitrosamines.

Nitrosamines can be observed/formed in the raw materials/solvents/water used in the API/drug product manufacturing process, excipients used during the manufacture of drug product, or even the primary/secondary packaging systems used to deliver the product.

• In the recent years pharmaceutical industry has become aware of the threat that nitrosamines pose and have initiated taking corrective measures for identification and estimation of nitrosamines in their products.
• Small nitrosamines in particular pose a greater threat to life as they can easily rupture the DNA and induce carcinogenicity. As days passed the guidelines became more and more stringent and the allowable intake of small nitrosamines is in ng/gm/day (sub ppb levels). High end instruments such as High-resolution mass spec and GCMS are used extensively to detect such nitrosamines in ppb levels.
• Further, the guidelines have proposed the risk-based approach to thwart the presence of nitrosamines in any of the sources stated above. In cases where theoretical risk assessment cannot prove the presence/absence of nitrosamines; practical testing of nitrosamines is mandatory to negate the presence of such toxic moieties.
• Pharmaceutical industry is constantly evolving giving control strategies and answering to the changes needed in the manufacturing process, change in excipients/solvents and even the packaging systems which do not pose threat to the living populace.

Challenges Ahead

While progress is being made, the pharmaceutical industry still faces several challenges in eliminating nitrosamine contamination completely:

• Complex Manufacturing Processes: Pharmaceutical manufacturing involves numerous steps, with many opportunities for contamination at various points. Identifying and controlling all potential sources of nitrosamines can be daunting, especially for drugs with complex formulations or multi-step manufacturing processes.
• Supply Chain Issues: With the global nature of the pharmaceutical supply chain, ensuring that every raw material and ingredient meets safety standards can be challenging. Variability in raw materials or inconsistent supplier practices can contribute to nitrosamine formation.
• Cost and Time Constraints: Implementing the required testing, reformulation, and redesigning manufacturing processes to meet new standards often requires significant investment in time and resources. This can be especially challenging for smaller pharmaceutical companies.
• Greater collaboration among various regulatory bodies, pharmaceutical industry and supply chain is mandatory to avert the increasing threat of nitrosamines that industry is facing.

Work done at Simson Pharma related to nitrosamines

• Simson Pharma is a leading provider of nitrosamine impurities.
• Simson Pharma provides practical assessment of plausibility of nitrosamines in APIs/drug products.
• As an alternative to practical testing, Simson pharma also provides theoretical testing of nitrosamines assessing API ROS and solvents/chemicals used; closed container system, excipients used in formulations (in case of drug product)
• Provide comprehensive report for plausibility of nitrosamines in API or drug product.