How to Characterize your Biotech Impurity in 3 steps

ToxBy.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, …)