The Pig-a assay: Our experiences with the standalone and integrated (repeat-dose toxicology and TGR) study design

UKEMS 2023 -- The in vivo phosphatidylinositol glycan class A (Pig-a) gene mutation assay is based on the endogenous X-linked Pig-a gene, which codes for an N-acetyl glucosamine transferase that is involved in the biosynthesis of glycosyl phosphatidyl inositol (GPI) anchor for tethering a variety of mammalian cell surface protein markers. OECD test-guideline 4701 was published in June 2022 and there is growing interest in integrating the assay into both transgenic rodent studies2 (TGR Muta?Mouse) and repeat-dose general toxicology studies. The Pig-a assay at Labcorp has been validated in the rat, mouse and Muta?Mouse with sufficient data generated to compile historical control ranges for each, which are presented. The assay has been performed as a standalone study, integrated into repeat-dose general toxicology studies or our Muta?Mouse studies. Pig-a analysis has also been conducted alongside both peripheral blood micronucleus (PBMN) and comet end-points. Here we discuss our experiences with the assay, the challenges of both designs and specific considerations when integrating into general toxicology studies.