Industry and regulators are evaluating the use of rapid adventitious virus detection methods, i.e. next generation sequencing (NGS), to replace or supplement current test methods, specifically animal tests. Most NGS applications, currently discussed in context of Viral Safety of Biologics, e.g. efforts of the “Advanced Virus Detection Technologies Interest Group” (AVDTIG), focus on unbiased deep sequencing of novel host cells, gene therapies, viral vectors and vaccine products. A molecular NGS based method is especially beneficial for products that require neutralization prior to testing, to prevent product interference in cell culture based infectivity assays, detecting virus contaminants. A targeted NGS Viral Safety assay can be a useful tool for in-process testing, to enable forward processing decisions, and mitigate the business risk of a facility contamination. Shortening FIH (first in human) timelines, the time from cell substrate generation to release of first drug product (DP) batches, is a common challenge in manufacturing of protein therapeutics in mammalian cell culture, i.e. CHO processes. Tests for detection of adventitious agents, both mycoplasma and adventitious virus, are 28 day assays, and are considered a critical step on FIH timelines. The industry is moving to PCR based mycoplasma testing, since such assays have gained acceptance of Health Authorities, and provide results in a significantly shorter time. At this time, there is no regulatory acceptance for replacing the current indicator cell culture based adventitious virus assay with a rapid molecular method; batch release supporting testing requires the compendia test. Nevertheless, it should be possible to use a rapid method capable of detecting a wide range of potential viral contaminants to detect such contaminants at an earlier stage of the process, and to enable forward processing decisions, i.e. release of a master cell bank for drug substance (DS) manufacture, and release of DS batches for DP conversion. Bristol Myers Squibb participates in an early access study, evaluating a targeted NGS-based adventitious virus test specific for viral contaminants of CHO cell cultures, developed by Thermo Fisher Scientific.
Upon completion, the participant will be able to understand the importance of adventitious agent testing in bio-manufacturing, for patient safety and business risk mitigation
Upon completion, the participant will be able to explain difference between unbiased and targeted rapid adventitious agent tests
Upon completion, the participant will be able to define applications for unbiased and targeted testing