The cliff-edge of toxicological concern: highlighting the potential issues of an over-reliance on "less-than-lifetime" thresholds.

The Threshold of Toxicological Concern (TTC) is a very well-established concept in applied toxicology, and has become a key tool for the pragmatic human health risk assessment of data-poor chemicals. Within the pharmaceutical sector, regulatory guidance on genotoxins defaults to a TTC of 1.5 μg/day equating to a maximum lifetime cancer risk of 1 in 100,000.

Assessment of Biomolecule Reactivity with Leachables.

Leachables in pharmaceutical products may react with biomolecule active pharmaceutical ingredients (APIs), for example, monoclonal antibodies (mAb), peptides, and ribonucleic acids (RNA), potentially compromising product safety and efficacy or impacting quality attributes. This investigation explored a series of models to screen extractables and leachables to assess their possible reactivity with biomolecules. These models were applied to collections of known leachables to identify functional and structural chemical classes likely to be flagged by these approaches.