CPHI Milan 2026: Nitrosamine Risk Mitigation, Part 1

Nitrosamine have been a problem in pharmaceutical manufacturing since approximately 2018, after the carcinogenicimpurities were found in statin drugs. Since then, regulators and pharmaceutical manufacturers have been working to mitigate the risk of nitrosamines in drugs.^1,2

PharmTech spoke with Bram Baert, Global Head of Regulatory Affairs at Capsugel, and Sandrine Picco, Senior Analytical Specialist on Capsugel's Innovaform Accelerator team, to find out about Capsugel’s approach to nitrite and nitrosamine risk ahead of their CPHI Milan 2026 presentation, “Nitrosamine Risk Mitigation: From Regulatory Expectations to Practical Implementation.”

According to Baert nitrite occurs naturally and often intrinsically in raw materials; therefore, driving it to zero is frequently impractical and can add significant manufacturing cost and complexity. Because many medicines can safely tolerate a defined amount of nitrite without meaningful risk, a better approach, according to Baert, is to determine the safety threshold for a given product, then ensure the excipient consistently stays below it. The goal, he said, is not the lowest possible number but a scientifically justified, risk-appropriate one.

Picco addressed why reducing nitrite risk requires more than analytical testing alone. Nitrite is a ubiquitous environmental trace contaminant found in excipients, APIs, manufacturing environments, and material surfaces, making control difficult given its varied origins and uneven distribution, Picco explained. While controlling raw materials and standardizing manufacturing are essential, Picco noted these steps aren’t sufficient on their own, because nitrite can also migrate from storage conditions and primary packaging.

On testing harmonization, Picco cautioned that nitrite numbers alone can mislead, because results vary considerably between batches and even between labs testing the same batch. Meaningful comparisons require first understanding how the data were generated: whether the method was validated and fit for purpose, how samples were stored, and what comparison standards were applied.

CPHI Milan is being held October 6-8, 2026 in Milan, Italy. Baert and Picco’s presentation will occur on October 7 at 2:15 PM in the Supply & Formulation Excellence Theater. Visit Lonza Capsugel at booth 1A2.

Click on the video above to watch part 1 of the 2-part 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.