A new study from Merck Healthcare KGaA and Lek Pharmaceuticals (a Sandoz company) explains why some medicines might contain small amounts of harmful nitrosamines, which are substances that can form during the manufacturing process. The researchers found that the levels of nitrite—a key ingredient in these impurities—in common pill-making materials, called excipients, are not always the same. Instead, they can change based on exposure to air pollution, such as nitrogen oxides (NOₓ), which are gases often found in the air. This means nitrite levels in these materials aren’t fixed; they can vary depending on the environment where the materials are stored or handled. Recently, tests have shown that nitrite in excipients can lead to the formation of nitrosamines, which are a concern for drug safety. Because of this, some manufacturers have started labeling their excipients with their nitrite content or even offering special “low-nitrite” versions. However, the study found that even these low-nitrite options might not always keep nitrite levels low enough in the final medicine. This is because other factors in the manufacturing process, like how tablets are coated, also play a role in controlling nitrosamine levels. The study also discovered that some excipients are better at absorbing nitrite from the air than others. For example, basic carbonate-type excipients (a type of ingredient) can trap nitrite without it turning into nitrosamines, making them safer in this regard. On the other hand, ingredients like starch or cellulose, which are commonly used in many medicines, might absorb moderate amounts of nitrite and could be a bigger concern because they are used in large quantities. The study also pointed out that the way air moves through the manufacturing process—such as during drying, mixing, or coating tablets—can introduce nitrosamine risks. These activities may expose materials to more nitrogen oxides, increasing the chance of nitrosamine formation. Additionally, handling small samples in labs can accidentally expose them to air, raising nitrite levels and causing unexpected test results. To minimize this, the researchers recommend keeping materials that are sensitive to air pollution covered or sealed. While the study provides useful insights into how different ingredients and processes affect nitrosamine risks, the researchers note that their findings are relative and not exact measurements. They advise drug manufacturers to carefully assess the risks of their medicines by looking not just at the initial nitrite levels of the ingredients, but also at the manufacturing process and the properties of the ingredients themselves. The findings are expected to be published in the Journal of Pharmaceutical Sciences in November 2026.