Bioanalytical assays in support of tanezumab developmental and reproductive toxicity studies: challenges and learnings.

Bioanalytical challenges were encountered during developmental and reproductive toxicity studies of tanezumab in cynomolgus monkeys. Possible changes in breast milk composition over the postpartum period potentially complicated assessment of tanezumab concentration in this matrix, requiring validation of the quantification assay across different time intervals. Immunogenicity assessment in maternal serum was complicated by apparent increases in the incidence of antidrug antibody-positive results in treatment-naive samples as pregnancy progressed that were due to changes in the concentration of nerve growth factor, tanezumab's target protein. This was overcome by employing gestational day-specific cut points throughout pregnancy. Researchers should recognize potential challenges associated with dynamic matrices/physiological conditions and anticipate that assays developed under normal conditions may require adaptation for specialized situations.