Evaluation of a Reporter Gene Assay for Bioactivity Determination of Therapeutic Interferons through a Collaborative Study

摘要

Accurate determination of therapeutic interferon bioactivity is critical to ensure efficacy and avoid toxicity. Antiviral assay (AVA) is currently used to determine interferon bioactivity but AVA has inherent limitations including biohazard risk, complex procedure, and considerable variability between and within assays. Our previous study suggested that a reporter gene assay (RGA) was an efficient method with better repeatability, reproducibility and capability of determining the bioactivity of native and variant forms of therapeutic interferons. However, the RGA was not validated through multi-site trials, which could significantly impede its practical application to routine bioactivity determination of interferons. Here, four institutes were enlisted in a collaborative study utilizing a battery of statistical analysis techniques. We evaluated inter-and intra-laboratory precision and reproducibility, with the degree of agreement between two methods evaluated using Bland-Altman plot. The comprehensive statistical analyses of data generated from all participants not only revealed high degree of agreement between the RGA and AVA within each lab but also remarkable consistency across all participants. This work provides strong evidence that RGA could be a viable alternative for the bioactivity determination of active interferons, which would be a great progress in quality control of pharmaceutical interferons.