Nitrosamine impurities moved from an obscure toxicology concern to a filing requirement in the space of about three years. Regulators now expect a documented risk assessment for every product, and confirmatory testing wherever that assessment does not rule the risk out.

The sequence regulators expect

The order matters. Testing without a risk assessment behind it looks like a laboratory exercise rather than a control strategy.

  • Risk assessment across the API route, the excipients, the packaging and the process water
  • Confirmatory testing where a risk is identified or cannot be excluded
  • A control strategy for anything found above the acceptable intake
  • Stability data showing the impurity does not grow over shelf life

Why the detection limits are so low

Acceptable intake limits for nitrosamines are set in nanograms per day, which for a high-dose product can mean a specification in the low parts per billion. That rules out conventional HPLC and puts the work on LC-MS/MS or GC-MS/MS with careful attention to blank contamination, because nitrosamines are ubiquitous at trace level in the laboratory environment itself.

What to send us

Twenty units of the finished dosage form or 25 g of API, the certificate of analysis, and the risk assessment if you have already done one. The risk assessment tells us which nitrosamines to look for, which is the difference between a targeted method and an expensive fishing expedition.

Held under our CDSCO drug testing licence and GLP approval, so the data stands in a filing.