Viral Safety Testing Using an Advanced next Generation Sequencing and Bioinformatics Platform

Viral safety testing is a critical part of the Chemistry, Manufacturing and Control (CMC) of biologics throughout the development and release of commercial products. A major safety risk to humans and a financial burden for biopharmaceutical companies, viral contamination can arise from the contamination of cell substrates or the adventitious introduction of a virus during production. Covance and PathoQuest investigated the value and capabilities of a flexible Next Generation Sequencing (NGS) and bioinformatics platform to detect and identify adventitious virus contamination, conducting the following studies: ▶ NGS & PCR comparison using human plasma spiked with medium-titer viruses to detect viral contamination ▶ A blind study of minute virus of mice (MVM) infected/non-infected 324K cells co-culture to detect a very low-rate virus ▶ 324K cells infection with MVM to reveal raw material contamination and kinetic comparison of NGS & PCR ▶ Detection of SV40 transcripts (cell engineering) in the 324K cell line As a result, we recommend a dual approach for robust biosafety testing, with broad-scale NGS screening and bioinformatics to test for known and unknown adventitious agents complemented by targeted virus detection assays, such as PCR.