How to Characterize your Biotech Impurity in 3 steps

Tox by Design Risk Assessment methodology involves:

Step 1 − Identification of active substance synthesis or degradation impurities

  • Known impurities
  • Potential impurities

Step 2 − Hazard assessment and classification

  • bibliographic review
  • in silico studies: QSAR
  • classification in one of the 5 ICH M7 classes

Step 3 − Toxicological evaluation and risk evaluation

If the impurity is genotoxic (ICH M7 class 1 and 2), the methodology will follow ICH M7 guideline:

  • The Threshold of Toxicological Concern (“TTC”, 1.5 µg/day) or Less Than Lifetime (“LTL”, depends on the treatment duration of the drug) will be applied.

If the impurity is not genotoxic/mutagenic (ICH M7 class 4 and 5):

  • Determination of the toxicological profile of the impurity (CMR, acute toxicity, chronic toxicity, etc.) by studying literature data or by using in silico models (QSAR, Read across)
  • Calculation of a toxicological limit (Permitted Daily Exposure “PDE”)

In case of classification into ICH M7 class 3:

  • a bacterial methodology assay with the impurity alone can be conducted
  • the toxicological evaluation have to continue until risk characterization is completed in order to determine a threshold value (PDE, TTC, …)


You can check Tox by Design methodology for Out of Specification reassessment, which are duly validated and signed by an European Registered Toxicologist expert.

In the event you are performing this exercise for innovative compounds GMP scale up manufacturing, please be noted that Tox by Design is duly accredited for the French Research Tax Credit CIR.

Feel free to contact us using the Quotation Request below to receive a quotation for Out of Specification reassessment, before or after Marketing Authorisation.