Quality Control Testing for Adventitious Agents

Adventitious Agent (AA) testing is the technique used to assay for contaminating agents (e.g., bacteria, viruses, fungi) that are unintentionally introduced during the manufacturing of biotherapeutics and vaccines. While most agents are benign, some can be harmful and even deadly. Traditionally, AA testing has been performed using a combination of in vitro and in vivo assays. These long-standing techniques suffer from three major drawbacks:

1. Targeted: These approaches require some prior knowledge of the agents.
2. Large Sample Input: They require a large input of sample.
3. Low Throughput: They have a low level of high-throughput capability.

Next-generation sequencing (NGS) is a global approach that can multiplex multiple samples for a single sequencing run, accommodating up to 600+ samples at a time. It requires only 100 ng – 1 µg of DNA/RNA as input for sequencing library preparation. NGS can overcome all three pitfalls of traditional AA testing methods. Additionally, an NGS-based approach can identify novel adventitious agents, where traditional methods have historically failed.