LAUSR

Abstract A computational investigation into pregabalin lactamization has been recently published, confirming that the reaction depends on pH and allowing a reasonable pathway for the formation of the impurity pregabalin lactam (prega-L) to be proposed. However, without proof or regulatory criteria, that investigation assumed that the impurity pregabalin lactam (prega-L) has high toxicity potential, which is worrisome. The present communication reports on the preliminary assessment of the prega-L toxicity by computational methods. The principles outlined in the ICH guidance M7 are followed, and statistics- and rule-based methodologies (in silico models) are used; the mutagenicity potential is considered as endpoint, and implications for qualifying this impurity in drug substances and/or drug products are discussed.