Nitrosamine impurities in medicines

HSA has been closely monitoring international developments on the global issue of nitrosamine impurities in medicines. We are working closely with international regulatory agencies and product registrants to investigate the root causes of the impurities and to identify the necessary measures to address the issue.

Background

In mid-2018, several blood pressure medicines were recalled globally due to the presence of the nitrosamine impurity, N-nitroso-dimethylamine (NDMA). Since then, other medicines have been found to contain NDMA or other nitrosamine impurities. The source of nitrosamine impurities may be related to the medicines’ manufacturing processes, its chemical structure, and/or contamination issues.

What are nitrosamine impurities?

Nitrosamines are probable carcinogens based on animal studies. In these studies, animals were exposed over a prolonged period to amounts of nitrosamine impurities that are much higher than usual human exposure. The risk of cancer is with long-term exposure. There is no immediate risk associated with the use of medicines containing trace levels of nitrosamine impurities.

Nitrosamines can also be found in food, drinking water, the environment and in tobacco products. For example, NDMA can be found in low levels in processed food such as pickled vegetables, salted fish, processed meat products such as bacon and sausages.

A very conservative approach is used to set limits for these impurities in medicines, based on what is considered as reasonably safe if a patient takes the affected medicine every day for a lifetime of 70 years. Taking a medicine that contains nitrosamine impurities at or below the acceptable level is not expected to increase the risk of cancer. 

Patients are advised to speak to their doctor or healthcare professional if they have concerns about this issue and should not stop the medicines which has been prescribed to them for their medical conditions on their own. Sudden stopping of the medicines may pose a greater and more immediate health risk than the potential exposure to nitrosamine impurities.

What we are doing

As part of the regulatory approach to manage the issue, we have required product registrants to conduct assessments of their products for risk of nitrosamine impurities. Where nitrosamine impurities are identified, companies are required to determine the source of the impurities, conduct testing on their products, remove products that contain nitrosamine impurities above the acceptable levels and make the necessary changes to mitigate the risk.

We will continue to work with international regulatory agencies and companies to investigate and address the issue. Necessary actions will be taken to safeguard public health and to ensure patients’ continued access to essential medicines.

Further information