Nitrosamine impurities in medicines – Information for sponsors and manufacturers

TGA

The Therapeutic Goods Administration (TGA) is working closely with other international regulators and medicine sponsors to investigate and address nitrosamine impurities in medicines.

This page includes relevant information for all medicine sponsors and manufacturers, including those seeking to register new products. Sponsors should also be familiar with the significant amount of information published on nitrosamines from international regulators including the European Medicines Agency (EMA), US Food and Drug Administration (FDA) and Health Canada.

The TGA continues to collaborate with our international regulatory partners to investigate the issue of nitrosamine impurities in medicine products. This includes sharing information, determining the actions which may be required and coordinating efforts on inspections, risk assessments and communications. We recognise the benefits of international alignment of the approach to this issue where possible. The TGA will share information with industry should a new risk be identified, and take appropriate regulatory actions including overseeing the implementation of improved manufacturing and testing processes to ensure the safety and quality of medicines in Australia.

Long-term exposure over a period of years to nitrosamines that exceed certain levels can increase the risk of developing cancer. Given this, the aim is to eliminate or minimise the levels of nitrosamines present in affected medicines, as their presence is generally considered unacceptable from both quality and safety perspectives. The TGA has set acceptable intake (AI) limits for many nitrosamine impurities to ensure medicines remain both safe and of high quality. The limits are used to determine if regulatory actions are required for affected products.

A range of regulatory responses can be used to manage this issue, including medicine recalls, suspending medicines, placing conditions on a product’s registration and/or actions related to product manufacture. When considering the appropriate regulatory response, the TGA also considers the impact on medicine availability.

Recall actions are available on the TGA System for Australian recall actions database. Safety advisories are published on the TGA website. Medicine shortages are published on the TGA Medicine shortage reports database.

Updated information will be published on this issue as it becomes available.

Australian medicine sponsors are responsible for the quality, safety and efficacy of their medicines, including the active ingredients, excipients and other raw materials used in the manufacturing of finished products. After registration, there are ongoing requirements for sponsors to monitor the quality, safety and efficacy of their products, as well as to inform the TGA if they become aware of any issues. This includes monitoring for emerging global issues and for global regulatory actions that may be relevant to Australia.

Sponsors should be aware of the global issue relating to nitrosamine impurities in medicines. Sponsors are required to inform the TGA in writing as soon as they become aware of information that indicates that the quality, safety or efficacy of their goods is unacceptable. This includes both sponsors and manufacturers of medicines and biologicals informing the TGA if they become aware that their medicine is affected by a nitrosamine impurity exceeding the appropriate AI limit. Sponsors should consult the TGA recalls

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