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.