Q: Why have nitrosamines become such a significant issue in the pharmaceutical industry?
A: Nitrosamine impurities have become a major concern in the pharma industry due to their potential as carcinogens. The issue gained prominence in 2018 when they were found in certain blood pressure medications, leading to product recalls. As a result, global regulatory authorities, including the FDA and EMA, now require comprehensive nitrosamine risk assessment for all drug products and APIs. It is no longer sufficient to just test for their presence in the final product; a proactive approach is required to understand and control the risk of their formation throughout the entire pharmaceutical manufacturing process.
Q: What are the primary risk factors for nitrosamine formation?
A: There are three key factors that, when present together, increase the risk of nitrosamine formation. First, a secondary amine must be present, which could be in the API, a degradation product, or a trace contaminant. Second, the environmental conditions must be conducive to the reaction, such as specific temperature, pH, or concentration. Finally, a nitrosating agent, like nitrites, must be present. Nitrites can be a hidden source of risk, found in solvents, recycled materials, or even excipients used in the final drug formulation.
Q: How does Lonza help its clients assess and mitigate nitrosamine risk?
A: At Lonza, we have developed a structured, science-driven process to identify, evaluate, and mitigate risks. Our risk management strategy begins with a simple screening step to identify amine groups. If they are present, we conduct a detailed paper-based assessment using data from excipient suppliers to estimate potential nitrite levels. This helps us to determine if a product's acceptable intake limit could be exceeded. If a risk is identified, we work with our clients to implement a confirmatory testing and mitigation strategy, which may include process changes, reformulation, or alternative packaging to ensure patient safety and regulatory compliance.
Q: Is it enough to just test for nitrosamines at the end of the manufacturing process?
A: No, it's not. The key is to embed the nitrosamine risk assessment process early in drug development. Nitrosamines can form or increase over time under certain storage conditions, so a comprehensive strategy goes beyond final product testing. It involves understanding the entire product lifecycle and implementing controls well before process performance qualification. This proactive approach ensures that risks are managed sustainably, protecting both the product and the patient. Partnering with a CDMO like Lonza can help you navigate these regulatory challenges and accelerate your development with confidence.