WHO/BS/2014.2247 Collaborative Study to Establish the First WHO IS for Detection of Hepatitis C Virus Core Antigen

Overview

A Collaborative Study was carried out to develop an international standard for Hepatitis C virus (HCV) core antigen for use with HCV core antigen detecting assays. The candidate standard is a lyophilized plasma preparation obtained from a donor infected with HCV genotype 1a. Twelve laboratories from nine countries world-wide participated in the collaborative study to evaluate and characterize the candidate material (sample A) using the assays in routine use in their laboratory alongside with the corresponding liquid-frozen bulk material (sample B) and four liquid frozen neat and diluted HCV core antigen positive plasma specimen (samples C to F). Six assays were used including two quantitative and one qualitative HCV Ag assays as well as three qualitative HCV Ag/Ab combination assays. The assays´ analytical sensitivities were determined to assess the potency and compared to the corresponding liquid bulk material. The results showed considerable differences in analytical sensitivity between the various assays yielding an endpoint titer range from 1:2 for the least sensitive assay to 1:3200 for the most sensitive assay. The same differences in sensitivity between the assays as with the candidate standard A were reflected by samples C to F. Intralaboratory and inter-laboratory variability for sample A and the bulk material sample B were in an expected range for immunoassays and it can therefore be assumed that the candidate material was still homogenous after the lyophilization step.

Overall, the study results show that there was good comparability of sensitivity for HCV core antigen between the various assays and laboratories by the candidate standard sample A. The potency of the candidate standard material is however dependent on the sensitivity of the test kits. It was therefore decided to determine the units based on highest sensitivity

Accelerated and on-going real-time stability studies of the proposed 1st WHO International Standard for HCV core antigen indicate that the preparation is stable and suitable for longterm use when stored as recommended.

It is therefore proposed that the candidate material (PEI code 129096/12) is established as the 1 st WHO International Standard for HCV core antigen for use with HCV core antigen assays with an assigned potency of 3,200 International Units per mL (IU/mL) when reconstituted in 0.5 mL of distilled water.