Singapore Health Sciences Authority (HSA) has updated the webpages on nitrosamine impurities in medicines.
The main webpage provides general information on the background and the regulatory approach on the nitrosamine impurities issue. The three subpages are:
1. List of impacted medicines – Provides information on the list of therapeutic products recalled due to nitrosamine impurities as well as the list of therapeutic products for which HSA has temporarily allowed the use of a higher interim acceptable intake to avoid supply disruptions to patients.
2. Guidance for product registrants – Provides information on the actions required by product registrants to manage the issue.
3. Test methods – Provides the test methods developed by HSA for the identification and determination of nitrosamine impurities in therapeutic products.
Question-and-answer document for product registrants on management of nitrosamine impurities in therapeutic products
Please refer to the following link for:
– the main webpage and subpages as mentioned above: https://www.hsa.gov.sg/therapeutic-products/medicines-quality-and-compliance-monitoring/nitrosamine-impurities-in-medicines
– question-and-answer document as mentioned below: https://www.hsa.gov.sg/therapeutic-products/medicines-quality-and-compliance-monitoring/nitrosamine-impurities-in-medicines/guidance-for-product-registrants
HSA has also developed a question-and-answer document to provide further details and clarify on HSA’s current approach, recommendations, and regulatory requirements for managing nitrosamine impurities in therapeutic products to support product registrants in addressing this issue. The document covers the following topics:
• Risk assessment
• Acceptable intake
• Product testing, root cause analysis and CAPA development
• Requirements for new and pending applications
Five appendices to the Q&A document have also been developed:
1. Appendix 1: HSA recommended acceptable intake for certain known nitrosamines – Lists the acceptable intakes that are recommended by HSA for certain known nitrosamines.
2. Appendix 2: Assessment aid for assessing nitrosamine risk – Serves as a guide to facilitate the assessment for the risk of nitrosamine in a product.
3. Appendix 3: Guidance on submission of nitrosamine risk assessment where a risk is identified – Outlines the minimum data required in a nitrosamine risk assessment report if a risk of nitrosamine formation has been identified.
4. Appendix 4: Carcinogenic Potency Categorisation Approach (CPCA) for nitrosamines – Describes the approach for assigning a nitrosamine impurity to a predicted carcinogenicity potency category, with a corresponding acceptable intake, based on an assessment of activating or deactivating structural features present in the molecule.
5. Appendix 5: Enhanced Ames test (EAT) conditions for nitrosamines – Describes the enhanced testing conditions for the Ames assay for nitrosamines.
The Q&A document and the associated appendices will be updated as new information becomes available. HSA recommends that product registrants should keep up to date with the latest information and evolving international regulatory requirements on this topic.