Ask the Expert: Understanding the Latest Science and Customer Needs on Nitrosamine Risk Mitigation

• Since the discovery of nitrosamine contaminants in pharmaceuticals in 2018, implementing mitigation strategies has become a primary concern for drug manufacturers. With emerging new science estimating that nitrosamine contamination is more common than previously thought and looming deadlines set by the FDA, formulation specialists need to be able to confidently address nitrosamine risk mitigation.
• In our latest ask-the-expert interview, Zdravka Misic, Principal Scientist, and Bruna Matteucci, Business Development Manager at dsm-firmenich, discuss the latest scientific developments in the field of nitrosamine risk mitigation and elaborate on learnings from collaborating with customers.

The discovery of nitrosamine contaminants in commonly used drug products in 2018 shook the pharmaceutical industry and made formulation and reformulation for low nitrosamine content a key topic for drug manufacturers. Since then, there have been many scientific and regulatory developments that are paving the way for companies to follow. We interviewed leading experts from dsm-firmenich, Zdravka Misic (Principal Scientist), to discuss the latest science emerging from the field of nitrosamine risk mitigation and Bruna Matteucci (Market Development Manager Pharma), to explore important touch points for customers navigating the nitrosamine mitigation process. Read on to gain valuable insights from our conversation with the experts.

What are the latest scientific findings in managing the risk of nitrosamine formation in drug products and possible mitigating strategies?

Since the discovery of nitrosamines in Ranitidine, Valsartan and Metformin, additional research has been conducted to assess the presence of such contaminants in other pharmaceutical products. The latest estimates from a large in-silico study have predicted that the risk of nitrosamine contamination in regularly prescribed drug products is more common than previously thought, with 40.4% of active pharmaceutical ingredients (API) and 29.6% of API impurities being classified as potential nitrosamine precursors.¹ Furthermore, recent evidence has identified certain types of packaging as sources of nitrosamine contamination and new nitrosamine impurities within sitagliptin medicines.^2,3

Despite the growing concerns about nitrosamine impurities in pharmaceuticals, there have been positive findings pointing towards an effective solution to mitigate contamination. Two studies have conducted a screening of known nitrite scavengers and investigated their effectiveness against nitrosamine formation. 45 These studies have shown that antioxidants, particularly ascorbic acid, can be used to mitigate nitrosamine formation effectively.

What are the main concerns customers are facing in the mitigation process?

Nitrosamine mitigation is a process that requires pharmaceutical companies to evaluate the risk associated with each drug product and develop a safe and reliable mitigating strategy that meets the regulatory standards. This already challenging process is accompanied by the looming deadline, as most companies will have to present mitigation strategies by the end of the year. Our conversations with customers have revealed three primary concerns in the context of nitrosamine risk mitigation:

1. Regulations. Customers are looking for more information on the Food and Drug Administration (FDA) guidelines and European recommendations to manage the risk of nitrosamine contamination in human drug products.
2. Strategy. Customers want to understand how antioxidants can be part of their mitigation strategy and how effective they are at inhibiting nitrosamine formation.
3. Formulation. Many customers express the need for technical support for new drug formulations and concern regarding the impact of reformulation on the final drug product effectiveness and safety.

How can dsm-firmenich support customers with different requirements?

dsm-firmenich supports its customers with the reformulation of existing and formulation of new drug products. Depending on the level of support required, DSM offers:

• High-quality pharma grade antioxidant excipients – ascorbic acid and alpha-tocopherol – proven to effectively inhibit nitrosamines and act as a stabilizer in the finished drug product formulation.
• GMP-certified ingredients that comply with USP/EP/JP standards and supported by the necessary documentation (including DMFs and CEPs).
• Regulatory insights, guidance, and the ability to manage market entry registration processes.
• Extensive knowledge in formulation and technical expertise.

dsm-firmenich offers tailored solutions to customers for their individual portfolios, whether their drug product is already on the market or in development.