EMA Considers Ways to Evaluate Non-Genotoxic Drug Impurities

Drug sponsors should assess the safety of non-genotoxic impurities (NGIs) in chemically synthesized drugs on a case-by-case basis, the EMA’s Committee for Medicinal Products for Human Use suggests in a draft reflection paper released for stakeholder comment.

For assessing risk, “a reasonable first step could be to assess whether the exposure to the NGI would remain below a threshold of toxicological concern,” the paper recommends. When this is the case and it can be corroborated that no relevant pharmacological activity would occur, the evaluation could end.

When a risk can’t be excluded on the basis of negligible exposure, sponsors can get information from toxicological databases, or using toxicological techniques such as read-across — a technique for predicting endpoint information for one substance  by using data from the same endpoint from another substance.