Case example: Nitrosamine impurities in medicines challenge the authorities and industry

Nitrosamines are chemical compounds, some of which are classified as carcinogens. Nitrosamines have been found in, e.g. food and medicines. EU guidelines and operating models for the management of the potential health risk caused by them in medicinal products have been published since 2018.

EU authorities have set general limit values for nitrosamines that must not be exceeded in medicinal products. The limit values are intended to ensure that the cancer risk associated with nitrosamines is less than 1/100,000 for people taking a medicine for life. It is the responsibility of the marketing authorisation holders of medicinal products (pharmaceutical companies) to create a strategy to prevent and limit the formation of nitrosamines in the manufacturing and storage processes of medicinal products. In addition, the marketing authorisation holders shall assess the presence of nitrosamines in medicinal products and report identified nitrosamines impurities to the authorities. If necessary, efforts should also be made to improve manufacturing processes.

Nitrosamines impurities are visible to patients as shortages of medicines

The challenge of nitrosamines has been more extensive than expected. The current operating model requires a lot of resources from all parties, both the authorities and the industry. The operating model causes disruptions in the supply of medicines and slows down the market introduction of new medicines. Availability problems caused by supply disruptions are visible throughout the health care chain, all the way to patients. 

The operating model causes disruptions in the supply of medicines and slows down the market introduction of new medicines.

Studies show that not all nitrosamines have mutagenic effects, making it impossible to treat them as one group of carcinogenic chemicals.  Problems have also emerged in finding and validating a suitable toxicological test method, so that a negative test result can be accepted as evidence of a lack of mutagenicity.

Fimea assembled an expert group to solve the challenge

In 2022, Fimea assembled an internal expert group across organisational boundaries to solve the challenge of nitrosamines. The group identifies challenges related to nitrosamines, such as problems related to the availability of new and old medicinal products and the resource challenges of industry and authorities. The group also discusses the management of nitrosamine impurities and tries to find solutions to the identified problems. The expert group wrote a letter presenting challenges related to the management of nitrosamines impurities and suggestions for solving them. In January 2023, the letter was sent to various EU working groups to launch discussions on possible new approaches to addressing the nitrosamine challenge in the EU.

The expert group wrote a letter to the various EU working groups, in which challenges related to the management of nitrosamines impurities and suggestions for solutions were presented.