CPHI Milan 2026: Nitrosamine Risk Mitigation, Part 2

PharmTech spoke with Bram Baert, Global Head of Regulatory Affairs at Capsugel, and Sandrine Picco, Senior Analytical Specialist on Capsugel's Innovaform Accelerator Team, ahead of CPHI Milan to discuss the mitigation of nitrosamine risk. Nitrosamines were discovered in statin drugs in 2018,^1,2 and since then, regulators and drug manufacturers have been designing ways to analyze products for nitrosamines and to manufacture products in a way that limits the potential for nitrosamines. According to Baert and Picco, mitigating nitrosamine risk requires assessing each product individually, using sensitive analytics.

Picco notes that agents other than nitrite can trigger nitrosation, and nitrosamines have formed even when no nitrite was detected. Any excipient that poses a potential risk for a given API should therefore be carefully evaluated and kept at the lowest possible nitrite level, with the risk assessed case by case based on the API and the formulation. The industry now works at parts-per-billion (ppb) levels rather than parts-per-million (ppm), according to Picco, and theoretical assessments don’t account for environmental factors. As a result, controlling raw materials isn’t enough, she says. Manufacturing, handling, and storage conditions must also limit nitrosamine formation across the product life cycle.

Because nitrite is everywhere in the environment, Picco says a zero-nitrite strategy is practically impossible. Manufacturers should instead rely on sensitive, robust analytical methods and control the sources of variability, including raw material quality, differences between suppliers, and process parameters.

Baert adds that a drug product’s nitrosamine potential depends on how its raw materials, formulation, manufacturing process, and packaging interact, so the acceptable nitrite level differs from product to product. The nitrite level of each product should be designed and then consistently controlled to that level, Baert suggests. He stresses that the risk can’t be assessed in isolation. API and excipient manufacturers, formulation, manufacturing, analytical, quality, and regulatory teams, and packaging suppliers must all contribute to capture the full risk to patients.

Click the video above to watch the interview.

Click here for part 1 of this interview.

References

1. Zeleznik J, Badger S, Ghimire M. Excipient selection strategies to mitigate nitrosamine risk. PharmTech Ingredient Innovations eBook. April 8, 2026. https://www.pharmtech.com/view/excipient-selection-strategies-to-mitigate-nitrosamine-risks
2. FDA statement on the FDA’s ongoing investigation into Valsartan and ARB Class impurities and the agency’s steps to address the root causes of the safety issues. Press release. FDA. January 25, 2019.