Impact of drug concentration and ADA assay drug tolerance on the assessment and correlation of titer and signal to noise.

BACKGROUND/AIM: The three-tiered testing strategy for an anti-drug antibody (ADA) assay is a common practice for assessing the immunogenicity to therapeutic products. Efforts to streamline the ADA testing process led to proposals of using signal to noise (S/N) as a substitute for titer when determining ADA magnitude. This study aims to identify the critical factors that may influence the correlation of S/N and titer. METHOD/RESULT: Experimental and clinical ADA datasets were examined to assess how drug concentration and the assay drug tolerance affect the measurement and correlation of S/N and titer. Under various experimental conditions the influence of drug on titer was minimal across a range of drug concentrations. However, drug presence affected the S/N, particularly when drug concentrations approached the assay drug tolerance. Clinical ADA datasets showed a moderate to strong correlation between S/N and titer, demonstrating similar patterns of drug impact on both measurements, as observed in the experimental data. CONCLUSION: The presence of drug in clinical samples and the drug tolerance of the ADA assay simultaneously influence the measurement and correlation of S/N and titer. The fold difference between drug tolerance and the maximum drug concentration in samples is a key factor in determining this correlation.