FDA Requirement to inform about nitrosamine risk in ongoing/new clinical trials

Regulatory Intelligence
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Concerns: New FDA GL “Control of Nitrosamine Impurities in Human Drugs”

I am reaching out to the community to seek clarification on the following paragraph of FDA’s new guideline - I would be thrilled to learn your experience on this:
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My questions are:

  1. What exactly is a nitrosamine “risk”? Is it the mere presence or the presence above a certain FDA limit or the presence above a certain limit as defined by the sponsor (which may be higher than FDA)?
  2. What is the most appropriate form (e.g. IND update or dedicated letter) and timeline to inform the FDA?

Thanks!

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For new drugs, you are expected to perform the “risk” assessment like any other appoved drug, API, formulation, process, packaging etc., whatever applies. This should be done before the drug goes to humans. If your product has possibility of any nitrosamines, including NDSRIs, a strategy should be developed as soon as possible and FDA should be informed may be through a Type C meeting.

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To me, basically if you have a secondary amine in the product, you should check whether nitrosamines can form in your drug product. Ideally you should not expose people taking part on a clinical trial or a BE study to potential highly potent mutagenic impurities

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