Stacy L. Springs from the MIT Center for Biomedical Innovation presented at the NCM Biopharma Day in Boston on “Application of nanopore long-read sequencing to sterility testing for cell therapy products.” Springs spoke about the diversity of impurities in biological medicines. They spoke about the need for rapid sterility testing in cell therapy manufacturing. Springs described the CAR T cell therapy process and all the steps that need to be coordinated. The cells are very precious, and the detection of small numbers of viruses and bacteria in the background of cells is critical. A lead postdoc on this project worked on rapid metagenomic detection using long-read sequencing. They applied a machine learning model. He spiked into the T-cells bacteria and fungus. He performed 16S/18S rDNA PCR for Nanopore sequencing. The bioinformatics workflow included a host removal step to filter out host reads. Metagenomic classification uses a machine learning model and decision matrix. Within 16 hours, bacterial and fungal contaminants can be identified. The classifier is undergoing development to improve classification, particularly with negative controls. Springs also asked: why test for adventitious viruses in cell therapy products? Springs described an agnostic viral detection approach as challenging with host cell genomic information. They developed a concentration step and amplification workflow they called CoNS-seq. This approach reduced the limit of detection by three logs! This is the approach described in the talk that I watched last night. Springs concluded that this approach has great potential.
