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.

Ensuring the safety and integrity of biologics is paramount for pharmaceutical and biotechnology companies. Traditional adventitious agent (AA) testing methods, such as cell-based assays, in vivo animal studies, and PCR-based approaches, often suffer from limitations in sensitivity, specificity, and turnaround time. These methods can struggle with detecting novel agents and are resource-intensive. 
 
Next-Generation Sequencing (NGS) offers a significant advancement in AA testing. It provides broad-spectrum detection of both known and unknown adventitious agents with greatly increased sensitivity and faster results.^1,2 This comprehensive genetic analysis minimizes the risk of false negatives, streamlines remediation, and enhances overall product safety.³ 
 
The power of NGS lies in its speed and high-throughput capabilities. DNA/RNA isolation to library sequencing can be completed in a single day, with 30-100+ samples processed simultaneously. Unlike targeted PCR approaches, which are limited to detecting sequences with pre-designed primers, NGS offers an unbiased, global approach.⁴ It provides untargeted capture of biological sequences within a sample, making it a rapid, reproducible, and reliable method for identifying adventitious agents due to its extreme sensitivity. 
 
Our NGS-based adventitious agent testing provides a comprehensive and highly sensitive solution for your biologics. Leveraging deep sequencing, we rapidly detect a broad spectrum of known and unknown adventitious agents, providing a critical layer of confidence in your manufacturing processes. This sequencing-based approach minimizes false negatives and offers unparalleled insights into the genetic makeup of contaminants, facilitating swift and effective remediation. 
 
We are committed to quality and regulatory compliance. Our facility is actively gearing towards Good Manufacturing Practices (GMP) and Good Laboratory Practices (GLP) certifications. This dedication involves rigorous adherence to validated protocols, comprehensive documentation, stringent quality control, and continuous personnel training. Our goal is to provide testing services that exceed the industry’s highest standards for data integrity, reproducibility, and reliability. 
 
Partner with us to enhance your adventitious agent testing strategy. Our experienced scientists and state-of-the-art NGS platforms are ready to support your unique testing needs, from research and development to lot release. By choosing our NGS-based testing, you gain a powerful tool for risk mitigation, regulatory compliance, and ultimately, the assurance of product safety for patients worldwide. 
 
Khan, A. S., Mallet, L., Blümel, J., Cassart, J. P., Knezevic, I., Ng, S. H. S., Wall, M., Jakava-Viljanen, M., Logvinoff, C., Goios, A., & Neels, P. (2023). Report of the third conference on next-generation sequencing for adventitious virus detection in biologics for humans and animals. Biologicals, 83, 101696. https://doi.org/10.1016/j.biologicals.2023.101696  
Gombold, J., Karakasidis, S., Niksa, P., Podczasy, J., Neumann, K., Richardson, J., Sane, N., Johnson-Leva, R., Randolph, V., Sadoff, J., Minor, P., Schmidt, A., Duncan, P., & Sheets, R. L. (2014). Systematic evaluation of in vitro and in vivo adventitious virus assays for the detection of viral contamination of cell banks and biological products. Vaccine, 32(24), 2916-2926. https://doi.org/https://doi.org/10.1016/j.vaccine.2014.02.021  
Morris, C., Lee, Y. S., & Yoon, S. (2021). Adventitious agent detection methods in bio-pharmaceutical applications with a focus on viruses, bacteria, and mycoplasma. Current Opinion in Biotechnology, 71, 105-114. https://doi.org/https://doi.org/10.1016/j.copbio.2021.06.027  
https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-5-r2-viral-safety-evaluation-biotechnology-products-derived-cell-lines-human-or-animal-origin-step-2b_en.pdf