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2019 · 09ImpuritiesRegulatory Notices

Nitrosamine risk assessment initiated across the register

Ergopharm has initiated a structured nitrosamine risk assessment across its register, evaluating each product for routes by which such impurities could form or be carried over, following the industry-wide reviews that began in 2018.

Nitrosamine impurities changed how the industry thinks about impurity control. They arise not from the active substance itself but from combinations of conditions — a secondary or tertiary amine meeting a nitrosating agent under the right circumstances — which means they can appear in a process that has been running unchanged for years and has never been looked for.

These impurities do not come from the molecule. They come from the circumstances, which is why nobody was looking.

The assessment works route by route through each product: the synthetic steps of the active substance, the reagents and solvents used, recovered and recycled materials, excipients, packaging, and the storage conditions of the finished product. Where a theoretical route is identified, confirmatory testing is performed with methods sensitive enough to detect at the levels of concern; where none is identified, the reasoning is documented rather than left implicit.

The assessment is not treated as a one-off exercise. It is repeated when a supplier changes a process, when a new source of active substance is introduced, and periodically as part of the product quality review.

Key facts

Scope
Every product in the register
Examines
Synthesis, reagents, recovered materials, excipients, packaging, storage
Where a route exists
Confirmatory testing at levels of concern
Repeated
On supplier process change, new source, and periodic review

This notice describes Ergopharm’s own packaging and processes and how they follow published standards; it does not assert a specific national marketing approval.