# Nitrosamines impurities in medicines

Source: https://www.keypedia.com/records/uk_mhra_guidance/uk-mhra/bfd824d7-8986-4c81-a93a-955a2050dc0d
Type: Guidance
Published: August 24, 2023

> The Medicines and Healthcare products Regulatory Agency (MHRA) has issued a comprehensive framework regarding the risk of nitrosamine impurities in human medicinal products. This regulatory guidance applies to all pharmaceutical Marketing Authorisation Holders and manufacturing sites operating within the United Kingdom. Unlike a specific inspection report for a single company, this document establishes industry-wide standards to address the potential formation of nitrosamines, which are classified as probable human carcinogens. The main issues addressed include the chemical conditions during drug synthesis that lead to nitrosamine formation, such as the use of specific solvents, reagents, and raw materials. Contamination risks are also noted in relation to recovered materials or cross-contamination in multi-purpose facilities. Under the Human Medicines Regulations 2012, manufacturers are required to conduct thorough risk assessments of their production processes. Required actions involve a three-step approach: first, performing a risk evaluation to identify potential nitrosamine presence; second, conducting confirmatory testing if a risk is identified; and third, updating marketing authorizations to include mitigation strategies if impurities are detected above acceptable limits. The MHRA emphasizes that proactive monitoring and process validation are essential to ensure patient safety and product quality. Companies must maintain detailed records of these assessments for review during routine regulatory inspections to demonstrate ongoing compliance with these safety standards.

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## Content

The Medicines and Healthcare products Regulatory Agency (MHRA) has assessed the risk of nitrosamine formation or presence during the manufacture of human medicines and has provided guidance for manufacturers to avoid the presence of nitrosamine impurities.

## Attachments

- [Nitrosamines impurities in medicines](/government/publications/nitrosamines-impurities-in-medicines/nitrosamines-impurities-in-medicines)